Archives for July 2017

Newly Discovered Gene Variants Link Innate Immunity and Alzheimer’s Disease

(University of Pennsylvania School of Medicine) Three new gene variants, found in a genome wide association study of Alzheimer’s disease (AD), point to the brain’s immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, cells that are part of the brain’s injury response system. The study is an international collaboration of four AD research consortia that analyzed DNA from 85,000 subjects. The results are reported online this week in Nature Genetics.

Beta-amyloid plaques from an AD mouse model. Pink represents beta-amyloid deposits (plaques), brown represents microglia cells and blue/purple is nuclei of neurons and glial cells. Credit: Stefan Prokop, MD, Perelman School of Medicine, University of Pennsylvania

Studies of this type focus on identifying new therapeutic targets for treatment or prevention of AD, a goal of researchers world-wide. Genetic variation of the type described in this paper are “experiments of nature,” of a sort, that reveal when a specific gene is altered, disease risk can be affected.

“This is direct evidence that if drugs can be designed to target these proteins, we have a chance to alter disease risk in people,” said senior author Gerard Schellenberg, PhD, a professor of Pathology and Laboratory Medicine, and director of the Alzheimer Disease Genetics Consortium (ADGC) at the Perelman School of Medicine at the University of Pennsylvania.

“It’s been known for decades that microglia — a first-line-of-defense cell we are born with — surround amyloid plaque deposits associated with Alzheimer’s. These multiple gene ‘hits’ all originating from microglia are the clearest demonstration that these cells are part of Alzheimer’s pathology and, more importantly, provide clear protein targets where we can start to intervene with drugs.”

The ADGC, supported by the National Institute on Aging (NIA) at the National Institutes of Health, is one of the four consortia of the International Genomics of Alzheimer’s Project on this study. The others are Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE), European Alzheimer’s Disease Initiative (EADI), and Genetic and Environmental Risk in Alzheimer’s Disease (GERAD).

The variants the team found — PLCG2, ABI3, and TREM2 — are all protein-coding mutations in genes that are highly expressed in microglia and are part of an immune cell protein network where multiple components contribute to AD risk. One of the genes, PLCG2, is an enzyme that is a potential drug target.

Key questions remain in how microglia should be targeted and whether the injury response should be inhibited or activated and at what stage of disease.

“Since prevention is a key goal of therapy, influencing microglial cells before onset of cognitive changes needs to be explored,” Schellenberg said.

The three variants they identified are fairly rare and he accounts for their success in finding them to their three-stage study. In the first stage, the entire protein coding regions of 34,290 samples were sequenced. In the second and third stages, the team further refined the sequences of variants and verified the significant hits against untested samples from AD patients.

“Our findings show that microglia and the innate immune system — via microglia — directly contribute to susceptibility of late-onset Alzheimer’s disease, and are not just a down-stream ‘after-the-fact’ consequence of damage to the brain,” Schellenberg said.

Citation

https://www.sciencedaily.com/releases/2017/07/170717110511.htm

Journal Reference
Gerard D Schellenberg et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nature Genetics, 2017; DOI: 10.1038/ng.3916

University of Pennsylvania School of Medicine. (2017, July 17). Newly discovered gene variants link innate immunity and Alzheimer’s disease: Findings give neurologists fresh ideas for enlisting immune system to fight Alzheimer’s. ScienceDaily. Retrieved July 27, 2017 from www.sciencedaily.com/releases/2017/07/170717110511.htm

 

Emergency and Urgent Hospitalizations Linked to Accelerated Cognitive Decline in Older Adults

(Rush University Medical Center) Emergency and urgent hospitalizations are associated with an increased rate of cognitive decline in older adults, report researchers at Rush University Medical Center. The results of their study suggest that hospitalization may be a more of a major risk factor for long-term cognitive decline in older adults than previously recognized.

“We found that those who have non-elective (emergency or urgent) hospitalizations and who have not previously been diagnosed with dementia or Alzheimer’s disease had a rapid decline in cognitive function (i.e., thinking abilities) compared to the prehospital rates,” said Bryan James, PhD, an epidemiologist and in the Rush Alzheimer’s Disease Center and an assistant professor in the Rush Department of Internal Medicine.

“By comparison, people who were never hospitalized and those who had elective hospitalizations did not experience the drastic decline in cognitive function.”

James and colleagues presented the research data at the Alzheimer’s Association International Conference in London on July 17.

Study compares hospitalization data and cognitive assessments for 930 older adults

The data emerged from a study of 930 older adults (75 percent female, an average age of 81 years old) enrolled in the Rush Memory and Aging Project (MAP) in Chicago. The study involved annual cognitive assessments and clinical evaluations.

Information on hospitalizations was acquired by linking records of 1999 to 2010 Medicare claims for these participants with their MAP data. All hospital admissions were designated as elective, emergency, or urgent (the latter two were combined as non-elective for analysis). Non-elective hospitalizations thus include emergencies and admissions for conditions that require immediate attention.

Of the 930 participants, 613 were hospitalized at least once over an average of almost five years of observation. Of those who were hospitalized, 260 (28 percent) had at least one elective hospital admission, and 553 (60 percent) had at least one non-elective hospital admission. These groups included 200 participants (22 percent) who had both types of hospitalizations.

Non-elective hospitalizations were associated with an approximately 60 percent acceleration in the rate of cognitive decline from before hospitalization. Elective hospitalizations, however, were not associated with acceleration in the rate of decline at all.

‘Elective admissions do not necessarily carry the same risk’

“We saw a clear distinction: non-elective admissions drive the association between hospitalization and long-term changes in cognitive function in later life, while elective admissions do not necessarily carry the same risk of negative cognitive outcomes,” James said.

“These findings have important implications for the medical decision making and care of older adults. While recognizing that all medical procedures carry some degree of risk, this study implies that planned hospital encounters may not be as dangerous to the cognitive health of older persons as emergency or urgent situations.”

This work expands upon previous research which has shown that after being hospitalized, older adults are at high risk for memory and other cognitive problems, including both transient (temporary) delirium and long-term changes in cognition, including dementia. According to the Healthcare Cost and Utilization Project in October 2010, 40 percent of all hospitalized patients in U.S. are age 65 and older. Therefore, hospitalization may be an under-recognized risk factor for cognitive decline and dementia for a large number of older adults that deserves more attention.

Detection of dementia at the earliest stages has become a worldwide priority, because drug treatments, prevention strategies and other interventions will likely be more effective very early in the disease process, before extensive brain damage has occurred. Research results reported at the Alzheimer’s Association International Conference provide clues about associations between cognitive status in older people and several behavior and lifestyle factors, including verbal skill, hearing, dental health, and hospitalization.

“It is essential that we learn more about factors that impact risk for Alzheimer’s disease and other dementias, especially lifestyle factors that we can change or treat,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer.

Citation

https://www.rush.edu/news/press-releases/emergency-and-urgent-hospitalizations-linked-accelerated-cognitive-decline-older

© Rush University Medical Center

 

 

Healthy Eating Habits May Preserve Cognitive Function and Reduce the Risk of Dementia

(Alzheimer’s Association) Results from four large population-based studies support a connection between good dietary practices and better cognition in old age. Study results were reported at the 2017 Alzheimer’s Association International Conference (AAIC 2017) in London.

A group of U.S. scientists found that, among nearly 6,000 older adults in the Health and Retirement Study, those who consistently followed diets long known to contribute to cardiovascular health were also more likely to maintain strong cognitive function in old age. They found that sticking to the specially designed MIND diet and Mediterranean diet was associated with 30 to 35 percent lower risk of cognitive impairment in healthy older adults. In fact, the investigators discovered that those with healthier diets exhibited meaningful preservation of cognitive function.

  • The Mediterranean and DASH (Dietary Approaches to Stop Hypertension) diets were originally developed or codified to help improve cardiovascular health.
  • A hybrid of these diets, called the Mediterranean-DASH Intervention for Neurodegenerative Delay, or MIND diet, is gaining attention for its potential positive effects on preserving cognitive function and reducing dementia risk in older individuals. A 2015 study found that individuals adhering to this diet exhibited less cognitive decline as they aged (Morris et al. Alzheimer’s Dement. 2015; 11:1015-22).

Other diet-related studies reported at AAIC 2017 included:

  • Researchers from the Karolinska Institute in Sweden found that – in a group of more than 2,200 older adults – people sticking to a Healthy Nordic Diet (including non-root vegetables, certain fruits, fish and poultry) enjoyed better cognitive status than individuals who ate a less healthy diet.
  • From more than 7,000 participants in the U.S.-based Women’s Health Initiative Memory Study, researchers found that older women who ate diets traditionally thought of as heart-healthy, in particular the MIND Diet, were less likely to develop dementia.
  • A team of researchers at Columbia University presented data suggesting that poor diet may promote premature signs of brain aging through inflammatory mechanisms, which were also associated with smaller brain volume.

“Although the idea that a healthy diet can help protect against cognitive decline as we age is not new, the size and length of these four studies demonstrate how powerful good dietary practices may be in maintaining brain health and function,” said Keith Fargo, PhD, Alzheimer’s Association Director of Scientific Programs and Outreach. “That said, we must understand that what we eat is just one part of the puzzle. Adapting our lifestyles as we get older – for example by exercising regularly, watching what we eat and engaging in lifelong learning – is important in order to maximize the potential to reduce risk of cognitive decline and dementia.”

The Alzheimer’s Association offers 10 Ways to Love Your Brain, including broad dietary guidance, based on the latest research.

Heart Healthy is Brain Healthy

Claire McEvoy, Ph.D. at the University of California, San Francisco, and colleagues examined the association between adherence to the Mediterranean and MIND diets and cognitive performance in a large, nationally representative population of 5,907 older, community-dwelling adults in the Health and Retirement Study. The researchers found that the more healthfully people ate, the better they functioned cognitively.

After controlling for demographic, lifestyle and health variables, participants who were highly adherent to these diets were 30 to 35 percent less likely to exhibit poor performance on a measure of cognitive function. Study participants who were moderately adherent to either diet were 18 percent less likely to exhibit signs of cognitive impairment.

Benefits of a Healthy Nordic Diet

Weili Xu, M.D., Ph.D., at the Karolinska Institute, Stockholm, and colleagues sought to identify dietary habits associated with preserved cognitive function in 2,223 community-dwelling, dementia-free adults in Sweden. The investigators found during six years of follow-up that even moderate adherence to a healthy diet known as the Nordic Prudent Dietary Pattern (NPDP) resulted in better cognitive status than individuals who ate a less healthy diet that included fatty foods, sweets and processed foods. In this population, NPDP was found to be a better predictor of preserved cognitive function than the MIND diet, Mediterranean diet, DASH diet and Baltic Sea Diet.

The NPDP included:

  • More frequent consumption of non-root vegetables, apple/pears/peaches, pasta/rice, poultry, fish, vegetable oils, tea and water, and light to moderate wine intake.
  • Less frequent intake of root vegetables, refined grains/cereals, butter/margarine, sugar/sweets/pastries, and fruit juice.

Women Who Eat Well Less Likely to Develop Dementia

Research published in 2015 found that the MIND diet was associated with a reduced incidence of Alzheimer’s disease in a sample of 923 older individuals (Morris et al. Alzheimer’s Dement. 2015; 11:1007-1014). Kathleen Hayden, Ph.D., Wake Forest School of Medicine in Winston-Salem, North Carolina, and colleagues sought to replicate these findings in 7,057 women participating in the Women’s Health Initiative Memory Study (WHIMS). Using data from WHIMS, they categorized the participants (mean age 71) into quartiles based on level of adherence to the MIND diet, with the 1st quartile being least adherent and the 4th being the most adherent. There were 615 incident cases of Alzheimer’s during a mean follow-up of 9.7 years.

Compared with women in the first (lowest) quartile of MIND adherence, WHIMS participants in the 2nd, 3rd, and 4th quartiles had 24 percent, 21 percent, and 34 percent reductions in the risk of developing Alzheimer’s. It is noteworthy that the largest share of the risk reduction occurred from the poorest dietary habits to the modestly adherent diet. These results corroborate results from previous research in smaller populations, and suggest that it may not require wholesale diet changes to help preserve the aging brain.

Poor Diet Linked to Inflammation

Building on solid evidence that eating well is brain healthy, researchers are beginning to explore mechanisms through which dietary mechanisms may influence cognitive status and dementia risk. Yian Gu, Ph.D., at Columbia University, New York, and colleagues examined whether an inflammation-related nutrient pattern (INP) was associated with cognitive function and structural MRI findings in the brain.

Using data on 330 community-dwelling, non-demented elderly individuals (mean age 79.7), the investigators found that an INP characterized by high intake of cholesterol, beta-carotene and lutein, and low intake of omega-3 polyunsaturated fatty acids, calcium, folate and vitamins (B1, B2, B5, B6, D, E), was positively associated with levels of inflammatory markers (C-reactive protein and interleukin-6). In addition, closer adherence to this INP was associated with smaller total brain gray matter volume and worse performance in executive function. Additional research in larger populations is needed to confirm the role of inflammation-related dietary components in brain and cognitive health, and help elucidate inflammatory or other mechanisms through which eating habits may alter brain function and structure.

While the U.S. Congress has recently provided additional funding for Alzheimer’s research at the National Institutes of Health, the commitment falls far short of the need. Congress must continue its commitment to the fight against Alzheimer’s and other dementias by increasing funding for Alzheimer’s research by at least an additional $414 million in fiscal year 2018.

About Alzheimer’s Association International Conference (AAIC)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2017 home page: www.alz.org/aaic/
AAIC 2017 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call +1 800.272.3900.

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  • Claire McEvoy, Ph.D., et al. Neuroprotective Dietary Patterns Are Associated with Better Cognitive Performance in Older US Adults: The Health and Retirement Study. (Funder(s): The Wellcome Trust)
  • Weili Xu, MD, Ph.D., et al. Which Dietary Index May Predict Preserved Cognitive Function in Nordic Older Adults? (Funder(s): CoSTREAM project; EU’s Horizon 2020 Research & Innovation Programme)
  • Kathleen Hayden, Ph.D., et al. The Mind Diet and Incident Dementia, Findings from the Women’s Health Initiative Memory Study. (Funder(s): National Institutes on Aging)
  • Yian Gu, Ph.D., et al. An Inflammatory Nutrient Pattern Is Associated Both Structural and Cognitive Measures of Brain Aging in the Elderly. (Funder(s): U.S. National Institute on Aging)
Citation

http://alz.org/aaic/releases_2017/AAIC17-Mon-Diet-Release.asp

 

Using Omega 3 Fatty Acids to Treat Alzheimer’s & Other Diseases?

(Louisiana State University Health Sciences Center) Understanding how dietary essential fatty acids work may lead to effective treatments for diseases and conditions such as stroke, Alzheimer’s disease, age-related macular degeneration, Parkinson’s disease and other retinal and neurodegenerative diseases. The key is to be able to intervene during the early stages of the disease.

That is the conclusion of a Minireview by Nicolas Bazan, MD, PhD, Boyd Professor and Director, and Aram Asatryan, PhD, postdoctoral researcher, at the Neuroscience Center of Excellence at LSU Health New Orleans School of Medicine published in the Journal of Biological Chemistry‘s Thematic Minireview Series: Inflammatory transcription confronts homeostatic disruptions.

Docosahexaenoic acid (DHA), a key essential Omega-3 fatty acid, produces signaling molecules called docosanoids in response to disruptions in the state of equilibrium within cells caused by injury or disease. Neuroprotectin D1 (NDP1) is a docosanoid that the Bazan lab discovered and found protects neurons by controlling which and how certain genes in the retina and brain respond.

Research shows that the preclinical events in Alzheimer’s disease including neuroinflammation, damage to dendritic spines — small doorknob-shaped protrusions that help transmit electrical signals to the cell — and problems with cell-to-cell communication coincide with decreased DHA content in the brain. The neuroprotective bioactivity of NPD1 includes inflammatory modulating properties as well as features that promote cell survival, both of which contribute to restoring a stable state of equilibrium, or homeostasis, within the cell.

In experimental models of stroke, researchers at LSU Health New Orleans Neuroscience Center led by Bazan have shown that the administration of NPD1 reduces the size of stroke damage and also saves tissue in the rim surrounding the stroke core, which remains viable for a short time.

Research has demonstrated that DHA from the liver is also retained and concentrated in photoreceptor cells and that retinal degeneration occurs when photoreceptor cells fail to capture DHA. When a gene that regulates the uptake of DHA is turned off, photoreceptor cells die and a single amino acid mutation in this receptor can cause retinitis pigmentosa.

Cells die through a variety of mechanisms. Contributors include a family of reactive oxygen species — compounds formed continuously as by-products of aerobic metabolism such as from reactions to drugs and environmental toxins, or when the levels of antioxidants are diminished creating oxidative stress, as well as inflammation and the disease process. Cell death is considered to be reversible until a first “point of no return” checkpoint is passed. The authors describe how NPD1 acts to stop cells from passing that checkpoint in cell death activation pathways including apoptosis, necrosis, necroptosis, pyroptosis, and pyronecrosis, among others.

The Minireview summarizes the effects of the essential fatty acid family member DHA and its bioactive derivative NPD1 in the context of a specific target of gene regulation. The authors also describe the mechanism of a pathway of regulation by a bioactive lipid that has a significant impact on cellular homeostasis — how NPD1 activates pro-survival genes and suppresses pro-death genes.

“The organizational and functional complexity of the brain raises new questions regarding how the cellular events described here operate in response to disrupted homeostasis to attain neuroprotection in pathological conditions,” notes Bazan.

“It is our hope that this knowledge will contribute to managing early stages of such devastating diseases as Alzheimer’s, stroke, traumatic brain injury, age-related macular degeneration, Parkinson’s and others.”

The research was supported in whole or in part by National Institutes of Health grants GM103340 from the National Institute of General Medical Sciences, EY005121 from the National Eye Institute, and NS046741 from the National Institute of Neurological Disorders and Stroke, as well as a grant from the Eye, Ear, Nose & Throat Foundation, and in part by an unrestricted departmental grant from Research to Prevent Blindness, Inc., New York.

Citation

http://www.lsuhsc.edu/newsroom/Using%20Omega%203%20Fatty%20Acids%20to%20Treat%20Alzheimer%E2%80%99s%20&%20Other%20Diseases.html

Journal Reference:

Aram Asatryan, Nicolas G. Bazan. Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection. Journal of Biological Chemistry, 2017; jbc.R117.783076 DOI: 10.1074/jbc.R117.783076

Copyright 2017, LSU Health Sciences Center New Orleans

 

Alzheimer’s Association International Conference 2017: Wrap Up

(Alzheimer’s Association) The Alzheimer’s Association today announced the launch of a $20 million U.S. two- year clinical trial to test the ability of a multi-dimensional lifestyle intervention to prevent cognitive decline and dementia in 2,500 older adults with no current cognitive symptoms but who are at increased risk for later cognitive decline. The announcement was made at the 2017 Alzheimer’s Association International Conference (AAIC 2017) in London.

The large U.S. study to PrOtect through a lifestyle INTErvention to Reduce risk (US POINTER) will include physical exercise, nutritional counseling and modification, cognitive and social stimulation, and improved self- management of medical conditions. Recruiting for the study will begin in 2018.

At AAIC 2014, Miia Kivipelto, M.D., Ph.D., Professor at the Karolinska Institutet, Sweden and the National Institute for Health and Welfare, Helsinki, Finland, and colleagues reported on the results of the FINGER Study – the first randomized controlled trial showing that it is possible to prevent cognitive decline using a multi-domain lifestyle intervention among older at-risk individuals. The results highlighted the value of addressing multiple dementia risk factors as a strategy to protect brain health. The FINGER model is now being replicated in the United States, Europe, Singapore, and Australia – including people from a variety of geographical and cultural backgrounds.

“We now can effectively prevent and treat heart disease with a combination of drugs and lifestyle. The same is true with some cancers; the same with HIV/AIDS. The same may also be true for Alzheimer’s disease and other dementias in the not too distant future,” said Maria C. Carrillo, PhD, Alzheimer’s Association Chief Science Officer.

“We must test all options to treat and prevent this horrible disease. We must find the answers for the millions dying with Alzheimer’s and their families, and the tens of millions more who will become affected if we do not act now. The Alzheimer’s Association is extremely proud to launch this clinical trial with our scientific partners,” Carrillo said.

Also announced today at AAIC 2017:

  • Interim results of the IDEAS Study, which is testing the impact on medical management of brain PET scans to detect amyloid protein. Amyloid forms the hallmark brain plaques of Alzheimer’s disease.
  • A possible blood marker for amyloid build up in the brain.
  • New insights into how amyloid and tau proteins spread through the brains of people with Alzheimer’s. Abnormal tau forms brain tangles – the other hallmark lesion of Alzheimer’s.

U.S. study to PrOtect through a lifestyle INTErvention to Reduce risk (US POINTER)

Increasing age is the greatest risk factor for Alzheimer’s disease. With the aging of the global population – and the slow progress of developing and testing drug treatments – prevention is pivotal in managing the inexorable rise in global cases of Alzheimer’s and other dementias.

In 2014, a large-scale two-year study in Finland in healthy older adults at increased risk of cognitive decline and dementia (the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, or FINGER Study) found that a two-year combination therapy involving physical exercise, nutrition, cognitive stimulation, and self-monitoring of heart health risk factors had a protective effect on cognitive function. These results were first reported at AAIC 2014 in Copenhagen.

According to Co-Principal Investigator Laura Baker, PhD, of the Wake Forest School of Medicine, Winston- Salem, North Carolina, the U.S. study to PrOtect through a lifestyle INTErvention to Reduce risk (US POINTER) is modeled on the FINGER study. It will test whether two years of a combined intervention that includes physical exercise, nutritional counseling and modification, cognitive and social stimulation, and improved self- management of medical co-morbidities benefits cognitive function in older adults at increased risk of cognitive decline and dementia. The comparison group will receive health education and support through in-person group meetings on health- and aging-related topics, and annual feedback on laboratory tests.

Starting in 2018, 2,500 study participants 60-79 years old will be identified using a medical record search to select those with medical conditions that have been linked to an increased risk for dementia (e.g., hypertension and other cardiovascular events, elevated blood sugar). Information about family history of Alzheimer’s, physical activity level, and current cognitive status and mood will be collected in follow-up interviews to further identify eligible participants. Local Alzheimer’s Association offices nationwide will participate in intervention delivery. National partnerships will be developed with community-based organizations to deliver the exercise, nutrition, social and medical aspects of the intervention.

The success of the intervention will be evaluated based on two-year change in a global measure of cognitive function focused on short-term memory, attention and concentration.

“As of now, there are no approved medications that have produced results similar to the FINGER Study. There is a pressing need to test the effectiveness of a multicomponent lifestyle intervention in larger and more diverse populations, such as the United States,” said Baker. “The lifestyle intervention in US POINTER is an important multi-dimensional strategy to protect brain health and potentially reduce risk of dementia.”

An update on FINGER and overviews of the Singapore (SINGER) and Australia (Maintain Your Brain) prevention studies will also be reported at AAIC 2017. The worldwide effort, collectively referred to as WW- FINGERS, supports a collaborative network of trials and experienced investigators to facilitate harmonization of research methods, and sharing of experiences and data for maximum global scientific impact.

Clinical Impact of Brain Amyloid PET Scans – Interim Results from the IDEAS Study

Launched in 2016, the four-year Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study is evaluating the impact of brain amyloid PET scans on patient management and health outcomes. Participants are more than 18,000 Medicare beneficiaries age 65+ with mild cognitive impairment (MCI) or atypical dementia who meet published Appropriate Use Criteria (AUC) for clinical amyloid PET. Before brain amyloid PET scans – which detect amyloid plaques, a core feature of Alzheimer’s – amyloid plaques could be seen only during autopsies, making it much harder to give living patients a definitive diagnosis.

At AAIC 2017, Principal Investigator Gil Rabinovici, MD, of the Memory and Aging Center, University of California, San Francisco, and colleagues reported early results from IDEAS assessing changes in patient management in the first 3,979 participants for whom case report forms were completed by participating dementia specialists both before and 90 days after the PET scans.

The pre-PET form documented the specialist’s management plan assuming no access to amyloid PET; the post- PET form recorded the medical management plan approximately 90 days after receiving results from a brain amyloid PET with an FDA-approved beta-amyloid imaging agent.

The researchers measured the rate of change between pre- and post-PET medical management, including one or more of: Alzheimer’s disease drug therapy, other drug therapy, and counseling about safety and future planning. Participants’ median age was 75 (range: 65-95); 64.4% were diagnosed with MCI, 35.6% met criteria for dementia. The most common suspected cause of cognitive impairment prior to PET was Alzheimer’s disease (76.3%). Rates of amyloid PET positivity were 54.3% in MCI and 70.5% in dementia.

Changes in medical management were seen in 67.8% of MCI patients (47.8% change in AD drugs, 36.0% change in other drugs, 23.9% changes in counseling), and in 65.9% of dementia patients (47.7% change in AD drugs, 32.2% change in other drugs, 15.3% change in counseling). Amyloid PET scans also reduced the need for additional diagnostic testing such as neuropsychological testing (from 26.3% recommended pre-PET to 11.0% recommended post-PET) and spinal fluid testing (from 10.5% to 1.0%).

“Our original hypothesis was that having amyloid PET scan results would change medical management in 30 percent of cases,” Rabinovici said. “Our interim results suggest we are well on track to see an effect of at least that magnitude, and perhaps greater, when the final results are available.”

“We look forward to reporting the results from the full study population. We are very grateful to the Centers for Medicare & Medicaid Services for their support of the IDEAS Study as our results indicate that access to this technology is making a real difference in the care of patients,” Rabinovici added.

The IDEAS Study is led by the Alzheimer’s Association and managed by the American College of Radiology.

The IDEAS Study was developed in response to CMS’ 2013 National Coverage Decision (NCD) on amyloid PET imaging in dementia and neurodegenerative disease (CAG-00431N) not to cover the scans because “the evidence is insufficient to conclude that the use of positron emission tomography (PET) amyloid-beta (Aβ) imaging is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of … Medicare beneficiaries with dementia or neurodegenerative disease.” Under the NCD, Medicare will provide coverage for one amyloid PET scan per patient enrolled in an approved clinical study.

A working group convened by the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) developed AUC for brain amyloid PET scans. The AUC indicate that amyloid PET should only be considered in patients with clear, measurable cognitive deficits when there is substantial diagnostic uncertainty after a comprehensive evaluation by a dementia specialist. According to AUC, amyloid PET may have greatest value in patients with either: (1) progressive, unexplained mild cognitive impairment (MCI); or (2) dementia of uncertain cause due to atypical or mixed symptoms, or unusually early age-of-onset.

A Blood Biomarker for Amyloid Plaques?

There is substantial evidence implicating amyloid-beta in the cause and/or progression of Alzheimer’s disease. Currently, a spinal tap or PET scan can detect deposition of amyloid in the brain, which precedes and increases the risk of progression to Alzheimer’s disease dementia. However, due to the invasiveness of a spinal tap and the radioactivity, limited availability and cost of PET scans, there is an urgent need for a simpler, more practical test for amyloid deposition, such as a blood test.

In order to investigate a blood-based amyloid biomarker, Randall Bateman, MD, and scientists at Washington University School of Medicine in St. Louis adapted their previously reported Stable Isotope Label Kinetics (SILK) method to measure amyloid in the blood – how fast it is created and how fast it is cleared away.

Participants were 41 older adults either with or without amyloidosis in the brain; they had either clinically diagnosed late-onset Alzheimer’s or were cognitively normal age-matched controls. All participants had brain PET amyloid imaging and/or cerebrospinal fluid (CSF) amyloid measures to detect brain amyloidosis. Blood sampling was conducted over 24 hours, and analyzed in a blinded fashion so researchers didn’t know which samples were from amyloid positive or amyloid negative people.

The scientists found the longer, stickier form of amyloid (known as Aβ42) was created and removed significantly faster in amyloid positive participants compared to amyloid negative participants. The findings were similar to prior studies done in CSF, suggesting that the amyloid levels detected in blood can accurately reflect the amyloid buildup in the brain. Additional results of a larger validation study will also be reported at AAIC 2017.

“These findings are important because they support the idea that blood amyloid interacts with and is derived from the brain,” Bateman said.

“We’re excited because the results also suggest that blood-derived amyloid-beta may be useful as a rapid and inexpensive screening test for brain amyloidosis, and may be able to identify people who are at higher risk of Alzheimer’s disease very early in the process.”

“Having a simple and inexpensive blood test for screening is likely to greatly accelerate clinical trials to find Alzheimer’s drugs. And, it could facilitate widespread treatment when effective anti-amyloid therapeutics are developed,” Bateman added.

“We envision that one day soon, as part of a regular screening for cholesterol and blood pressure, a person may also get a blood test to find out if the amyloid protein is building up in the brain, and then go on specific treatments to prevent the onset of Alzheimer’s disease dementia. This would be similar to the already successful approach of screening for and treating high cholesterol to reduce the risk of heart attacks and strokes.”

This research was supported by an Alzheimer’s Association Zenith award grant and an NIH R01 study.

Amyloid and Tau Spreading Pathways in the Brain, Correlated with Genetics

The ability to employ advanced imaging technology to “see” both of the hallmark proteins of Alzheimer’s (amyloid and tau) in the living brain is a significant recent advance in the field. It may prove to be transformational not only in our understanding of the disease and its progression but also in its potential to accelerate drug discovery.

According to Jorge Sepulcre, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, Boston, understanding the “spreading” phenomenon of abnormal tau and amyloid-beta proteins in the brain is critical to knowing what is causing the devastating cell damage and relentless symptoms of people with Alzheimer’s.

Sepulcre and colleagues developed a novel imaging approach to investigate the spreading pathways of tau and amyloid deposits over time, as well as their genetic vulnerabilities, in a longitudinal sample of elderly participants in the Harvard Aging Brain Study. Eighty-eight (88) study participants, average age about 76, were divided into two independent samples: (1) a cross-sectional sample of 69 people; and (2) a 1-2 year follow-up longitudinal sample of 19 subjects.

The researchers found that tau and amyloid appear to accumulate along distinctive pathways in the brain; the same communication pathways, or neural networks, we use for daily brain function. According to their findings, tau – which we know starts in the middle of the brain memory center – spreads forward and out toward the front of the brain. Amyloid, which starts in the back of the brain, spreads further back and outward from the middle. Specifically:

  • Medial/inferior temporal lobe areas project pathways of Tau-spreading toward anterior pole, lateral and posteriomedial temporal cortex, and orbitofrontal cortex.
  • Posterior cingulate cortex spreads Aβ toward surrounding areas and lateral parietal lobe.

The scientists discovered that 354 genes were significantly associated with the tau spreading pathway, including the MAPT gene, which was previously associated with Alzheimer’s disease risk. They also found 216 genes, including the CLU gene, significantly associated with the amyloid pathway. Additional analysis characterized the tau spreading genetic profile as “axon-related” and the amyloid-spreading genetic profile as “dendrite-related”. APOE, the gene with the highest impact on Alzheimer’s risk, was found to be the most central gene linking tau- and amyloid-spreading pathways.

“Our results reported at AAIC 2017 suggest that tau and amyloid advance through different brain systems over time,” Sepulcre said. “We also discovered certain genetic traits that may confer tau or amyloid vulnerability in the brain.”

“The findings may improve our ability to track responses to potential therapeutic interventions in the future,” Sepulcre added. “In addition, when more effective drug therapies become available, these results may help doctors determine which patients should get which therapies, and the optimum time to take them.”

About Alzheimer’s Association International Conference (AAIC)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2017 home page: www.alz.org/aaic/
AAIC 2017 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call +1 800.272.3900.

 

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  • Laura D. Baker, PhD, et al. U.S. Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (US- FINGER). (Funder: Alzheimer’s Association)
  • Gil D Rabinovici, MD, et al. Impact of Amyloid PET on Patient Management: Early Results from the IDEAS Study. (Funder(s): U.S. Center for Medicare and Medicaid Services, Alzheimer’s Association, Eli Lilly, GE Healthcare, Piramal)
  • Randall J Bateman, MD, et al. Concentrations and Stable Isotope Label Kinetics of Human Plasma Amyloid Beta. (Funder(s): U.S. National Institutes of Health, Alzheimer’s Association)
  • Jorge Sepulcre, MD, PhD, et al. In Vivo spreading Pathways of Tau and Amyloid Accumulation and Its Genetic Underpinnings. (Funder(s): U.S. National Institutes of Health, Alzheimer’s Association)
Citation
http://alz.org/aaic/releases_2017/AAIC17-Wed-briefing-Developing-Topics.asp?WT.mc_id=enews2017_07_19&utm_source=enews-aff-20&utm_medium=email&utm_campaign=enews-2017-07-19

 

 

The Lancet Commission: One Third of Dementia May Be Preventable

(Alzheimer’s Association) In a report presented today at the Alzheimer’s Association International Conference 2017 (AAIC 2017) in London, The Lancet International Commission on Dementia Prevention, Intervention and Care reported that more than one third of global dementia cases may be preventable through addressing lifestyle factors that impact an individual’s risk. These potentially modifiable risk factors have been identified at multiple phases across the life-span, not just in old age.

The Lancet Commission’s report was simultaneously published in The Lancet and presented at AAIC 2017.

Also at AAIC 2017, the U.S. National Institute on Aging (NIA) announced inaugural research grants to investigate health disparities in Alzheimer’s disease.

“Today’s findings are extremely hopeful,” said Maria Carrillo, PhD, chief science officer at the Alzheimer’s Association.

“At an individual level, many people have the potential to reduce their risk of cognitive decline, and perhaps dementia, through simple, healthful behavior changes. At a public health level, interventions based on this evidence could be extremely powerful in managing the global human and economic costs of Alzheimer’s disease and other dementias.”

The Alzheimer’s Association offers 10 Ways to Love Your Brain, including practical guidance to reduce your dementia risk based on the latest research.

The Lancet International Commission on Dementia Prevention, Intervention and Care

The Lancet Commission brings together 24 international experts to consolidate the huge strides that have been made in our knowledge and understanding of dementia risk factors, treatment and care, and the emerging knowledge as to what we should do to prevent and manage dementia. The Commission conducted a new review and meta-analysis; based on which they extended current models of risk by including hearing loss and social isolation. Incorporating potentially modifiable risk factors from across the life-span, they proposed a novel life- course model of risk, highlighting the opportunity for prevention.

Among their key recommendations are:

  • Be ambitious about prevention. Interventions for established risk factors may have the potential to delay or prevent one third of dementias.
  • Treat cognitive symptoms. To maximize cognition, people with Alzheimer’s dementia or dementia with Lewy bodies should be offered cholinesterase inhibitors at all stages, or memantine for severe dementia.
  • Individualize dementia care. Good dementia care spans medical, social and supportive care; and should be tailored to unique individual and cultural needs, preferences, and priorities.
  • Care for family carers. Family carers are at high risk of depression. Effective interventions reduce the risk and treat the symptoms, and should be made available.
  • Plan for the future. People with dementia and their families value discussions about the future and important upcoming decisions.
  • Manage neuropsychiatric symptoms. Management of the neuropsychiatric symptoms of dementia – including agitation, low mood or psychosis – is usually psychological, social, and environmental, with drug treatment reserved for more severe symptoms.
  • Consider end of life. A third of older people die with dementia, so it is essential that professionals working in end-of-life care consider whether a patient has dementia as they may be unable to make decisions about their care or express their needs and wishes.

Focus on Prevention

The Lancet Commission launched a novel life-span-based model of dementia risk, showing interventions that may maximize cognition, decrease distressing associated symptoms, reduce crises, and improve quality of life. The team estimate the contribution of each of the risk factors to the overall incidence of dementia, at the population level. The combined evidence to date shows that roughly 35 percent of all cases of dementia are attributable to nine potentially modifiable risk factors. Many of the risk factors occur at particular life stages but some, such as smoking and hypertension, are likely to make a difference at all life stages. The nine modifiable risk factors include:

  • Early life – Education to a maximum of age 15
  • Mid-life – Hypertension; Obesity; Hearing loss
  • Later life – Depression; Diabetes; Physical inactivity; Smoking; Low social contact

Risk factors that are more common account for a higher percentage of population risk. For instance, the authors estimate that eight percent (8%) of all dementia cases could be associated with poor early school education; and five percent (5%) could be associated with smoking. While the mechanism linking education, hypertension, diabetes and smoking to dementia is relatively well understood, the recognition of hearing loss as a potential risk factor is still new, and the research is at an earlier stage.

The Commission’s report delivered recommendations for targeted public health strategies that the researchers expect will significantly lower the global burden of Alzheimer’s and other dementias. For example:

  • The authors strongly recommend vigorously treating hypertension in middle aged and older people without dementia to reduce dementia incidence.
  • Other recommended interventions include more childhood education, getting regular exercise, maintaining social engagement, stopping smoking, and management of hearing loss, depression, diabetes, and obesity.

The authors stated that, due to lack of data, the study did not include dietary factors, alcohol use, visual impairment, air pollution and sleep.

“While public health interventions will not prevent, or cure all potentially modifiable dementia, intervention for cardiovascular risk factors, mental health, and hearing may push back the onset of many people for years,” said Professor Gill Livingston, MD, from University College London and lead author of The Lancet Commission.

“Even if some of this promise is realized, it could make a huge difference and we have already seen in some populations that dementia is being delayed for years. Dementia prevalence could be halved if its onset were delayed by five years.”

According to the Commission’s report, worldwide dementia prevalence could be reduced by more than 1 million cases with a 10 percent reduction in the prevalence of seven principal health and lifestyle factors. An intervention that delayed dementia by a year might decrease the number of people living with dementia globally by 9 million in 2050.

“Overall, there is good potential for prevention and, once someone develops dementia, for care to be high-quality, accessible, and give value to an underserved, growing population. Effective dementia prevention and care could transform the future for society and vastly improve living and dying for individuals with dementia and their families. Acting now on what we already know can make this difference happen,” said Lon Schneider, MD, from the University of Southern California and co-author of the Commission.

Advancing health disparities research in Alzheimer’s – National Institute on Aging inaugural grants

According to the Alzheimer’s Association 2017 Alzheimer’s Disease Facts and Figures, African-Americans are about twice as likely to have Alzheimer’s or other dementias as older whites, and Hispanics are about one and one-half times as likely to have Alzheimer’s or other dementias as older whites. Yet, these populations are underrepresented in Alzheimer’s and dementia research.

The NIA has identified a clear need to diversify research cohorts and improve methods and tools for conducting health disparities research related to Alzheimer’s disease and other dementias. Two funding opportunities were created to encourage research that examines disparities in Alzheimer’s disease using diverse cohorts of subjects. At AAIC 2017, NIA will announce the inaugural grant recipients and their projects, and highlight the new information expected to be generated because of these awards.

“Aging research using a framework that incorporate factors at multiple levels needs to be conducted with study populations that have robust demographic diversity,” said Carl V. Hill, PhD, MPH, Director of the NIA Office of Special Populations.

“When cohorts are diverse, new pathways that link environmental, sociocultural, behavioral and biological factors can be identified. This is our hope for these research awards.”

According to the funding opportunity announcements, health disparities populations include: Blacks/African Americans, Hispanics/Latinos, American Indians/Alaskan Natives, Asian Americans, Native Hawaiians and Other Pacific Islanders, Socioeconomically Disadvantaged Populations, and Rural Populations. Additional populations may include: Disability Populations, and Sex and Gender Minorities.

About Alzheimer’s Association International Conference (AAIC)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2017 home page: www.alz.org/aaic/
AAIC 2017 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call +1 800.272.3900.

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  • Gill Livingston, MBChB, PhD; Lon S. Schneider, MD, MS. The Lancet International Commission on Dementia Prevention and Care. (Funder(s): University College London, Alzheimer;s Society UK, Economic and Social Research Council, Alzheimer’s Research UK)
  • www.thelancet.com/commissions/dementia-2017
  • Carl V. Hill, PhD, MPH and Rachel Whitmer, PhD, chairs. Advancing Health Disparities Research with the National Institute on Aging (NIA). (Funder: U.S. National Institute on Aging)
Citation
http://www.alz.org/aaic/releases_2017/AAIC17-Thurs-briefing-Lancet-Global-health-policy.asp

 

Stressful Life Experiences Age the Brain by Four Years, African Americans Most at Risk

(Alzheimer’s Association) A series of studies reported at the 2017 Alzheimer’s Association International Conference (AAIC 2017) in London confirm racial inequities in numbers of people with Alzheimer’s disease and other dementias – even after age 90 – and also point to growing evidence that early life stress and neighborhood conditions contribute to dementia risk in late life.

One new study in Wisconsin found that a single major stressful event in early life is equal to four years of cognitive aging, and African Americans are most at risk – on average, they experience over 60 percent more of such events than non-Hispanic Whites over their lifetimes. A second study conducted by a health plan in Northern California found that African Americans born in states with the highest levels of infant mortality had 40 percent increased risk of dementia compared to African Americans not from those states, and 80 percent increased risk compared to Whites not from those states. Other studies reported at AAIC 2017 found:

  • Racial disparities in the risk for new cases of dementia previously observed in the younger elderly continue into the oldest-old (age 90+), which is the fastest-growing segment of the population. Researchers found oldest-old African Americans and Latinos had the highest incidence rates compared to Asian Americans and Whites – matching the overall patterns of racial/ethnic disparities in dementia seen in younger elderly. This is the first time different ethnicities in this older population group have been studied for risk of incident dementia.
  • Neighborhood disadvantage may contribute to observed disparities in prevalence of dementia.

“These studies were done with U.S. data, but they add weight to the global body of evidence around disadvantage and dementia risk, which is an issue governments around the world grapple with, and one that requires coordinated action,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer.

“For a racially diverse nation like the United States, and to address Alzheimer’s and dementia on a global scale, these findings support the need for targeted interventions, whether preventive or service-driven, to help address the gaps we know exist – and for more research.”

“In addition to research on Alzheimer’s risk factors and biology, the Alzheimer’s Association is particularly interested in increasing understanding of stigma and concern related to Alzheimer’s and other dementias in diverse communities,” Carrillo said.

Racial disparities in dementia continue into the oldest-old

In younger elderly (65 and older), there are marked differences in rates of dementia by racial/ethnic groups, showing increased rates for African Americans and decreased rates for Asian Americans. The Alzheimer’s Association 2017 Alzheimer’s Disease Facts and Figures reported that, for all adults 65 and older, African- Americans are about twice as likely to have Alzheimer’s or other dementias as older Whites and Hispanics are about one and one-half times as likely to have Alzheimer’s or other dementias as older Whites. However, it is not known if these discrepancies apply to the oldest-old (90 and older).

Rachel Whitmer, PhD, from Kaiser Permanente of Northern California (KPNC), and Maria M. Corrada, Sc.M., Sc.D., of the University of California, Irvine, and colleagues focused on 2,351 members of the KPNC health plan who, in 2010, were older than age 90 (avg. 93.1) with no diagnoses of dementia. Most of the study participants were women; the cohort was 72% White, 16% African American, 4% Latino, and 7% Asian American. The study looked at dementia diagnoses in the group made between 2010 and 2015, abstracted from electronic medical records.

The researchers found oldest-old Asian Americans have the lowest cumulative incidence (21%), followed by Whites (31%), Latinos (35%) and African Americans (39%) – matching the overall patterns of racial/ethnic disparities in dementia seen in younger elderly. In models adjusted for age as the time scale, education, sex, midlife and late-life vascular comorbidities, oldest-old African Americans had a 28 percent higher risk than oldest-old Whites. Compared to Asian Americans, African Americans had a 30% increased risk of dementia.

“Our results show that racial inequities in rates of dementia at younger ages continue after age 90,” said Whitmer, Senior Scientist at Kaiser Permanente Division of Research and senior author on the scientific abstract.

“These are the first estimates of dementia incidence in a diverse cohort of individuals age 90 and older. Given the increasing ethnic diversity in the coming decades, it is imperative to identify what factors contribute to the differences in rates, whether genetic, social, or lifestyle, as some of these factors may be modifiable.”

Lifetime stressful experiences worsen memory and thinking – more strongly in African Americans

Prevalence of Alzheimer’s disease and cognitive impairment is rising, and the greatest burden seems to be falling disproportionately on historically disadvantaged communities. Despite substantial evidence for racial disparities in later life cognitive health, specific causes remain unclear and the cognitive impact of lifelong adversity is underexplored.

Megan Zuelsdorff, Ph.D., at the University of Wisconsin School of Medicine and Public Health, and colleagues examined the impact of lifetime stressful experiences on cognition as part of the Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study. The study population included a total of 1,320 adults – African American (n=82) and non-Hispanic white (n=1,232); the goal was to understand how stressful experiences – such as being fired from a job, the death of a child, growing up with a parent who abused alcohol or drugs, or experiencing combat – impacted cognition differently in these two groups.

Average age, years of education, and APOEε4 status did not differ by race. Stressful experiences included educational difficulties, interpersonal conflicts, financial insecurity, legal/justice system issues, serious health events and psychosocial/physical trauma. Participants answered a questionnaire about stressful experiences and completed cognitive tests that measured memory and problem-solving abilities. Researchers stratified the sample by race and looked at stress-cognition relationships within African American and white subgroups.

A greater number of stressful events was associated with poorer late-life cognitive function for all study participants. Even within a relatively small, highly educated sample, African Americans experienced over 60 percent more stressful events than non-Hispanic Whites during their lifetimes, and these experiences were linked to poorer memory and thinking skills in older age. The researchers determined that, in African Americans, each stressful experience was equivalent to approximately four years of cognitive aging.

“Among African Americans in our study, adverse events across the lifespan predict cognitive function more strongly than established risk factors including age, education, and the APOE-e4 Alzheimer’s risk gene,” Zuelsdorff said.

“Adversity is a clear contributor to racial disparities in cognitive aging, and further study is imperative.”

Early life conditions – such as high infant mortality rates – may contribute to dementia risk in late life

High infant mortality rates are a marker of adverse social and physical conditions, and birth in areas with high infant mortality rates are associated with a variety of poor health outcomes. Yet, is unknown if birth in states with high infant mortality impacts dementia risk.

Paola Gilsanz, ScD, of the University of California, San Francisco, and Kaiser Permanente Division of Research, and colleagues looked at race specific infant mortality rates in 1928 of the birth states of more than 6,200 members of the Kaiser Permanente Northern California health system. Members born in the 10 states with highest rates of infant mortality for their race were categorized as being born in high infant mortality states. They linked this information with medical records to see if people born in high infant mortality states were at greater risk of dementia. They found that:

  • 1928 rates of infant mortality were much higher among African Americans (up to 277 deaths/1,000 live births) compared to Whites (up to 129 deaths/1,000 live births).
  • African Americans born in a state with a high infant mortality rate had a 40% higher risk than African Americans born in states without high infant mortality rates, even after taking into account education, high blood pressure in midlife, body mass index, stroke, and diabetes.
  • African Americans born in high infant mortality states had almost 80% greater risk of dementia even after accounting for education and health risk factors, compared to Whites born outside high infant mortality states.
  • Being born in a high infant mortality state was not associated with dementia risk among Whites.

“This is the first study of place of birth and long-term dementia risk,” Gilsanz said.

“African Americans born around 1928 were likely exposed to harsher early life conditions that may have increased their risk of dementia later in life. Our findings suggest that differences in early life conditions may contribute to racial inequalities in dementia rate, and they point to growing evidence that early life conditions contribute to dementia risk in late life.”

Living in a Disadvantaged Neighborhood may increase Alzheimer’s disease risk

Disadvantaged neighborhoods often pose barriers for accessing healthy foods, safe exercise options, toxin-free environments, and other factors that impact health. It is known that living in a disadvantaged neighborhood increases risk of diabetes, cancer, and early death, and that moving to less disadvantaged settings improves health.

Amy Kind, MD, PhD, of the University of Wisconsin School of Medicine and Public Health and colleagues used data from 1,479 people enrolled in WRAP. The scientists found the level of socioeconomic neighborhood disadvantage for each study participant using the Area Deprivation Index (ADI) score, which incorporates indicators of poverty, education, housing, and employment.

The researchers examined whether patterns of cognitive function and protein biomarkers (n=153 with spinal fluid samples) of Alzheimer’s were found more often in certain neighborhoods than would be expected to occur by chance alone. They found that people in the most disadvantaged neighborhoods had markedly worse cognitive performance in all aspects measured (working memory, immediate memory, speed and flexibility of cognition, and verbal learning), even after adjusting for age and education. They also had disproportionately higher levels of one Alzheimer’s disease biomarker in their spinal fluid (phosphorylated tau).

“This study provides evidence to suggest that living in a neighborhood challenged by poverty, low education, unemployment, and/or substandard housing may increase risk of Alzheimer’s disease, and may account for some of the observed differences in Alzheimer’s disease risk among people of different racial backgrounds and income levels,” said Kind.

Kind’s group has quantified ADI scores for more than 50 million neighborhoods across the United States and Puerto Rico; those results could be used to target dementia-focused intervention and research programs to areas of highest need.

While the U.S. Congress has recently provided additional funding for Alzheimer’s research at the National Institutes of Health (NIH), the commitment falls far short of the need. Congress must continue its commitment to the fight against Alzheimer’s and other dementias by increasing funding for Alzheimer’s research by at least an additional $414 million in fiscal year 2018.

About Alzheimer’s Association International Conference (AAIC)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2017 home page: www.alz.org/aaic/
AAIC 2017 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call +1 800.272.3900.

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  • Rachel Whitmer, Ph.D., Maria M. Corrada, Sc.M., Sc.D., et al. Racial/Ethnic Differences in Rates of Dementia Incidence Among the Oldest-Old (Funder(s): U.S. National Institute of Aging)
  • Megan Zuelsdorff, Ph.D., et al. Lifetime Stressful Experiences, Racial Disparities, and Cognitive Performance: Findings from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study. (Funder(s):U.S. National Institute on Aging, U.S. National Institute of Child Health and Human Development, Helen Bader Foundation, Northwestern Mutual Foundation, Extendicare Foundation, U.S. National Institutes of Health National Center for Advancing Translational Sciences)
  • Paola Gilsanz, Sc.D., et al. Birth in a High Infant Mortality State, Race, and Risk of Dementia (Funder(s): U.S. National Institute on Aging; UCSF Training for Research on Aging and Chronic Disease)
  • Amy J. Kind, M.D., Ph.D., et al. Neighborhood Socioeconomic Contextual Disadvantage, Baseline Cognition and Alzheimer’s Disease Biomarkers in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study (Funder(s): U.S. National Institutes of Health; U.S. National Institute on Aging; UW Institute for Clinical and Translational Research; William S Middleton Memorial Veterans Hospital Geriatric Research, Education and Clinical Center; University of Wisconsin Department of Medicine)
Citation

Abstract 19320 / Proposal ID O1-09-01

Public Health and Psychosocial: Epidemiology: Risk Factors for Dementia – A Life Course Approach Oral (AAIC), Sunday, July 16, 2017: 4:15-5:45 PM

Birth in a High Infant Mortality State, Race, and Risk of Dementia

Paola Gilsanz, ScD (paola.gilsanz@kp.org), Elizabeth Rose Mayeda, PhD, MPH3, Maria Glymour, ScD3, Charles P Quesenberry Jr., PhD2, Dan Mungas, PhD4, Charles S DeCarli, MD5 and Rachel A. Whitmer, PhD1,2 (1)University of California, San Francisco, San Francisco, CA, USA, (2)Kaiser Permanente Division of Research, Oakland, CA, USA, (3)UCSF School of Medicine, San Francisco, CA, USA, (4)University of California, Davis, Sacramento, CA, USA, (5)Department of Neurology, University of California at Davis, Davis, CA, USA

Background: Birth in high infant mortality states has been linked to poorer long-term health outcomes yet it is unknown if it impacts brain health in late-life. Adverse early life conditions may partially explain racial inequalities in rates of dementia, but thus far this has never been explored.

Methods: We evaluated 6,284 Kaiser Permanente Northern California health-plan members (17% Black, 83% White) born between 1919-1932 with health survey and clinical exam data collected between 1964-1973.

Clinical measures of midlife hypertension, BMI, and self-reported state of birth, race, and education were collected between 1964-1973. A birth state was categorized as a high infant mortality state (HIMS; yes versus no) if it was one of the 10 states with the highest rate of race-specific infant mortality in 1928. Dementia diagnoses (ICD-9 codes 331.0, 290.4x, 290.0, 290.1x, 290.2x, 290.3, 294.2x, and 294.8), stroke, and diabetes were abstracted from medical records 1/1/1996-10/1/2015. Cox proportional hazard models (age as time scale) evaluated associations of HIMS and dementia adjusted for sociodemographics and lifecourse vascular risk factors. Participants were censored at dementia diagnosis, death, health-plan membership lapse, or end of follow-up.

Results: 1928 rates of infant mortality were much higher among Blacks (median=116 deaths/1,000 live births; range: 65-277) than Whites (median=64 deaths/1,000 live births; range: 45-129). Adjusted for age and sex, HIMS birth was not associated with higher risk of dementia among Whites (adjusted Hazard Ratio (aHR)=1.01, 95% Confidence Interval (CI): 0.83-1.23). However, Blacks born in HIMS had 40% elevated risk (95% CI:1.02-1.91), which persisted after adjusting for education and comorbidities throughout the lifecourse (aHR=1.40, 95%CI:1.01-1.93). Compared to Whites born outside HIMS, Blacks born inside HIMS had almost 80% elevated dementia risk (aHR=1.79; 95% CI:1.31-2.44) adjusting for education and vascular comorbidities.

Conclusions: Infant mortality rates for Blacks in 1928 were much higher than that of Whites. In a cohort of elderly individuals, Blacks born in states with the highest levels of race specific infant mortality rates had 40% increased risk of dementia, though all individuals subsequently moved to California. Early life conditions may contribute to racial inequalities in dementia incidence and needs to be further investigated.

Abstract 14332 / Proposal ID O1-09-04

Public Health and Psychosocial: Title: Epidemiology: Risk Factors for Dementia – A Life Course Approach Oral (AAIC), Sunday, July 16, 2017: 4:15-5:45 PM

Lifetime Stressful Experiences, Racial Disparities, and Cognitive Performance: Findings from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study

Megan ZuelsdorffMegan Zuelsdorff, PhD1(mlzuelsd@wisc.edu), Carey E. Gleason, PhD2, Amy J. Kind, MD, PhD1,3, Rebecca L. Koscik, PhD4,5, Sterling C. Johnson, PhD4,6 and Ozioma C. Okonkwo, PhD2,4 (1)University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (2)Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (3)Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA, (4)Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (5)University of Wisconsin, Madison, Madison, WI, USA, (6)Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Background: Prevalence of Alzheimer’s disease and cognitive impairment is rising, and the greatest burden falls upon historically disadvantaged communities. Despite substantial evidence for racial disparities in later life cognitive health, underlying pathways are unclear and the cognitive impact of lifelong adversity remains underexplored. Stressful experiences cluster and accumulate across the life course, potentially fomenting cognitive health disparities. We examined relationships between lifetime stress and cognition among African American and non-Hispanic white adults in the longitudinal Wisconsin Registry for Alzheimer’s Prevention (WRAP) study.

Methods: Participants (N=1,320) reported lifetime stressful experiences and completed comprehensive neuropsychological testing. Cognitive outcomes included two executive function factor scores (Speed & Flexibility and Working Memory) and four memory scores (Immediate Memory, Verbal Learning & Memory, Visual Learning & Memory, and Story Recall). The key predictor of interest was a Lifetime Stress index score (sample range=0-17 experiences). Mixed-effects regression models, including socioeconomic and health covariates, were utilized to assess effects of lifetime stress in each cognitive domain. We stratified by race to explore between-group differences in stress-cognition relationships.

Results: Average age (mean=58.1, SD=6.5), years of education (mean=16.2, SD=2.8), and APOEε4 carrier proportion (38.5%) did not differ by race. However, African Americans (n=82) reported significantly more (mean=4.5) stressful experiences during their lifetime than non-Hispanic whites (n=1,232; mean=2.8, p<.001). In fully adjusted models including the full sample, lifetime stress partially attenuated negative relationships between African American race and both domains of executive function. Stratification revealed that cognitive detriment associated with lifetime stress in non-Hispanic whites is significantly potentiated among African Americans, for whom it is the strongest measured predictor of Speed & Flexibility (p=0.002) and Working Memory (p=0.03).

Conclusions: We found that lifetime stress is associated with poorer later-life cognition, particularly executive function, and contributes to racial disparities therein. Even within a small, highly-educated sample, African Americans report experiencing more stressful events and exacerbated stressor-associated cognitive dysfunction, with each reported experience equivalent to more than four years of cognitive aging. Our findings reaffirm the effect of stress on cognitive health and disparities, and emphasize the need to expand within-group, lifecourse-based strategies as we strive to eliminate disparities through targeted interventions.

Abstract 19427 / Proposal ID O1-04-02

Public Health and Psychosocial: Epidemiology: Social Disadvantage/Inequalities Oral (AAIC) Sunday, July 16, 2017: 2:00 PM-3:30 PM

Racial/Ethnic Differences in Rates of Dementia Incidence Among the Oldest-Old

Rachel A. Whitmer, PhD1 (Rachel.Whitmer@kp.org), Paola Gilsanz, ScD1, Claudia H. Kawas, MD2, Elizabeth Rose Mayeda, PhD, MPH3 and Maria M. Corrada, ScM, ScD2 (1)Kaiser Permanente Division of Research, Oakland, CA, USA, (2)University of California, Irvine, Irvine, CA, USA, (3)University of California, San Francisco, San Francisco, CA, USA

Background: By 2060 there will be 9.5 million individuals age 90+ in the United States and over one third will be Non-White. In younger elderly, there are marked differences in rates of dementia by racial/ethnic groups, showing increased rates for Blacks and decreased rates for Asians. However, it is completely unknown if these discrepancies also occur in the oldest-old.

Methods: We established a cohort of 2,351 members of Kaiser Permanente Northern California (KPNC) health-plan who, in 2010, were >age 90, with no diagnoses of dementia. Dementia diagnoses (ICD- 9 codes 331.0, 290.0-290.4x, 294.1, 294.2x, and 294.8) made in primary care, neurology, memory clinics, and psychiatry were abstracted from electronic medical records from 1/1/2010-12/31/2015. We estimated dementia incidence rates standardized to the 2000 US Census 90+ year- old population by race/ethnicity. Cox proportional hazard models (age as time scale) evaluated the association between racial/ethnic groups and dementia risk. Participants were censored at dementia diagnosis, death, >90 day gap in health plan membership, or end of study.

Results: The mean age in 2010 was 93.1 (range: 90-109). The cohort is 65% female, 72% White (N=1,702), 16% Black (N=375), 4% Latino (N=105) and 7% Asian (N=169). 771 members (32.8%) were diagnosed with dementia during the 5-year follow-up period. The mean age of dementia diagnosis was 95.48 (SE=0.10) and was similar across racial and ethnic groups: 95.56 (SE=0.11) for Whites, 95.21 (SE=0.23) for Blacks, 95.71 SE=0.66) for Latinos, 95.28 (SE=0.31) for Asians. The overall age-adjusted incidence rate (aIR) was 100.5 per 1,000 person-years. Asians had the lowest incidence rates (aIR=89.3), followed by Whites (aIR=97.0), Latinos (aIR=105.8), and, lastly, Blacks who had the highest rates (aIR=121.5). In cox proportional hazard models adjusted for age as the time scale, education, sex, midlife and late-life vascular comorbidities, Blacks had significantly higher risk (aHR=1.28; 95%CI: 1.05-1.51), compared to Whites.

Conclusions: These are the first estimates of dementia incidence in a diverse cohort of 90+ individuals. Patterns of racial/ethnic disparities in dementia seen in younger elderly continue after age 90. These estimates provide an important foundation for understanding the burden of racial disparities in dementia in the oldest-old, the fastest growing segment of the population.

Abstract 14725 / Proposal ID O1-04-03

Public Health and Psychosocial: Epidemiology: Social Disadvantage/Inequalities Oral (AAIC) Sunday, July 16, 2017: 2:00 PM-3:30 PM

Neighborhood Socioeconomic Contextual Disadvantage, Baseline Cognition and Alzheimer’s Disease Biomarkers in the Wisconsin Registry for Alzheimer’s Prevention (WRAP) Study

Amy J. Kind, MD, PhD1,2 (ajk@medicine.wisc.edu), Barbara B. Bendlin, PhD2,3,4, Alice J. Kim, BA1, Rebecca L. Koscik, PhD4, William R. Buckingham, PhD5, Carey E. Gleason, PhD3,4,6, Kaj Blennow, MD, PhD7,8, Henrik Zetterberg, PhD9,10,11, Cynthia M. Carlsson, MD3,4,6 and Sterling C. Johnson, PhD3,4,12,13 (1)University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (2)Geriatric Research Education and Clinical Center, Wm. S. Middleton Veterans Hospital, Madison, WI, USA, (3)Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (4)Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA, (5)Applied Population Laboratory, University of Wisconsin-Madison, Madison, WI, USA, (6)Geriatric Research Education and Clinical Center, W.S. Middleton Memorial Veterans Hospital, Madison, WI, USA, (7)Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden, Mölndal, Sweden, (8)Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden, (9)Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, (10)University College London, London, United Kingdom, (11)Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, (12)Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA, (13)Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Madison, WI, USA

Background: Dementia due to Alzheimer’s Disease (AD) disproportionately impacts racial/ethnic minorities and the socioeconomically disadvantaged—populations often exposed to neighborhood disadvantage. Neighborhood disadvantage is associated with education, health behaviors and mortality. Health improves with moving to less disadvantaged neighborhoods (Ludwig, Science 2012). Although studies have linked neighborhood disadvantage to diseases like diabetes and cancer, little is known about its effect on development of dementia.

Objective:To examine the association between neighborhood disadvantage, baseline cognition, and CSF biomarkers of AD among participants in the WRAP study, comprising a cohort of late-middle-aged adults enriched for parental family history of AD.

Methods: We created and validated neighborhood-level quantifications of socioeconomic contextual disadvantage for the full US—over 34 million Zip+4 codes—employing the latest American Community Survey and Census data. This metric—the Area Deprivation Index (ADI)— incorporates poverty, education, housing and employment indicators; predicts disparity-related health outcomes; and is employed by Maryland and Medicare through our provision. We used standard techniques to geocode all WRAP subjects with a documented address (N=1479). WRAP participants were ranked into deciles of neighborhood disadvantage, by ADI. Baseline cognitive function (indexed by factor scores) and CSF biomarker outcomes for levels of Aβ42 and P­tau181 (n=153 with CSF samples) were examined by neighborhood disadvantage decile.

Results: Higher levels of neighborhood disadvantage were associated with worse baseline cognitive outcomes, especially within the most disadvantaged neighborhood decile (p<0.0001). After adjustment for age and education, those within the most disadvantaged decile demonstrated worse cognitive performance across all domains (beta [95% confidence interval] and p-value by domain: working memory: -0.45 [-0.62, -0.28], <0.0001; immediate memory: -0.34 [-0.52, -0.17], <0.0001; speed/flexibility: -0.62 [-0.78, -0.45], <0.0001; verbal learning: -0.44 [-0.61, -0.27], <0.0001). Furthermore, subjects within the most disadvantaged neighborhood decile exhibited a mean CSF P-tau 11.61 units higher (p=0.064) than those within less disadvantaged neighborhoods. Aβ42 did not differ by neighborhood decile.

Conclusions: These early data suggest that neighborhood disadvantage may account for some of the observed disparities in prevalence of dementia. Given the urgent need to reduce dementia and AD disparities, the current results suggest that neighborhood disadvantage deserves additional study.

http://alz.org/aaic/releases_2017/AAIC17-Sun-briefing-racial-disparities.asp

 

New and Expanded Risk Factors for Cognitive Decline and Alzheimer’s Disease

(Alzheimer’s Association) Detection of dementia at the earliest stages has become a worldwide scientific priority because drug treatments, prevention strategies and other interventions will likely be more effective very early in the disease process, before extensive brain damage has occurred. Research results reported at the Alzheimer’s Association International Conference (AAIC) 2017 provide clues about associations between cognitive status in older people and several behavior and lifestyle factors, including verbal skill, hearing, and hospitalization.

“It is essential that we learn more about factors that indicate or impact risk for Alzheimer’s disease and other dementias, especially lifestyle factors that we can change or treat,” said Maria C. Carrillo, PhD, Alzheimer’s Association Chief Science Officer.

“The Alzheimer’s Association is committed to advancing scientific research to identify simple and accessible ways to spot the signs of cognitive decline.”

Having trouble with memory does not mean you have Alzheimer’s. That said, the Alzheimer’s Association says early detection allows people with dementia and their families:

  • A better chance of benefiting from treatment.
  • More time to plan for the future.
  • Increased chances of participating in clinical drug trials, helping advance research.
  • An opportunity to participate in decisions about care, living options, financial and legal matters.

Hearing loss is associated with poor cognition and progression to mild cognitive impairment

Taylor Fields, a doctoral student in the Neuroscience Training Program within the University of Wisconsin School of Medicine and Public Health, and colleagues examined the prevalence of hearing loss in late middle-aged adults with a family history of Alzheimer’s, and the association between hearing loss and cognitive status and decline. The researchers found evidence for a link between hearing loss and mild cognitive impairment, a condition that can be a precursor to Alzheimer’s disease.

The scientists used data collected from 783 people enrolled in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal study group of people with a parental history of Alzheimer’s. Participants undergo periodic tests to evaluate their ability to remember, process, and learn information. Study volunteers self-reported whether they had been diagnosed with hearing loss. At the beginning of the study, all volunteers had normal test results for clinical tests of cognitive function, and all were assessed for progression to mild cognitive impairment.

Over the course of four years, 72 (9.2 percent) study participants reported being diagnosed with hearing loss. Relative to those who reported normal hearing, people in the study with hearing loss were:

  • More likely to score significantly poorer on cognitive tests such as how quickly new information is processed, flexibility in thinking, and how the brain, eye, and hand coordinate during information processing.
  • Roughly three times as likely to be characterized as having mild cognitive impairment.

“This study suggests that hearing loss could be an early indicator of worsening cognitive performance in older adults,” Fields said.

“Identifying and treating hearing loss could have value for interventions aimed at reducing the burden of Alzheimer’s disease.”

Verbal fluency predicts cognitive health

In another analysis of participants in WRAP, Kimberly Mueller, PhD, of the Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, and colleagues investigated whether people with very early memory declines also show changes in their everyday speech. The researchers found that subtle changes in everyday speech, such as the use of short sentences, more pronouns, and pauses like “um” and “ah,” correlated with early Mild Cognitive Impairment (eMCI), which can be a precursor to Alzheimer’s disease.

In the study reported at AAIC 2017, the scientists analyzed two speech samples, taken two years apart, from 264 participants in WRAP. Of these participants, 64 were identified as having eMCI based on cognitive testing over 8-10 years. The speech samples, averaging one minute long, were collected by asking the participants to describe a simple picture.

Study participants with eMCI declined faster on two measures of speech: content and fluency. The content of their speech was less specific, with a higher proportion of pronouns to nouns (e.g., “she,” “it,” “them”). Their fluency was more disrupted (more hesitations, word repetitions, and filled pauses (“um,” “uh”)). Also, those with eMCI used less complex syntax and shorter sentences, and took more time to express the same amount of content as the cognitively healthy group.

“Our study is the largest prospective, longitudinal study of spontaneous speech samples in a study group of this kind,” Mueller said.

“We don’t know whether the eMCI group will go on to develop Alzheimer’s, so we will continue to follow them, and our next step is to repeat these analyses with participants who have other biomarker evidence, such as amyloid plaques and neurofibrillary tangles as seen on PET scans. Speech analysis may be a valuable cognitive marker to add to clinical assessments of cognitive function in the future.”

Emergency and urgent hospitalizations, but not elective admissions, are related to accelerated cognitive decline in older people

Research shows that older adults are at high risk for memory and other cognitive problems after being hospitalized, not only transient delirium but also long-term changes in cognition. However, it is unknown whether elective hospitalizations, such as for scheduled surgery, put older individuals at the same risk for faster cognitive decline as emergency or urgent admissions (nonelective hospitalizations).

In research reported at AAIC 2017, Bryan James, Ph.D., of the Rush Alzheimer’s Disease Center at Rush University Medical Center in Chicago, Illinois, USA, and colleagues found that nonelective hospitalizations were associated with acceleration in cognitive decline from prehospital rates, but elective hospitalizations were not associated with a change in the rate of cognitive decline. Data came from 930 older adults (75% female, mean age of 81 years old) enrolled in the Rush Memory and Aging Project (MAP) in Chicago.

The study involved annual cognitive assessments, as well as clinical evaluations. Information on hospitalizations was acquired by linking 1999-2010 Medicare claims records for these participants to their MAP data. All hospital admissions were designated as elective, emergency, or urgent (the latter two combined as nonelective for analysis).

Of the 930 participants, 613 were hospitalized at least once over an average of almost five years of observation. Of those who were hospitalized, 260 (28%) had at least one elective hospital admission, and 553 (60%) had at least one nonelective hospital admission; 200 participants (22%) had both types of hospitalizations.

In a model adjusted for age, sex, education, self-reported chronic medical conditions, length of stay, surgeries, intensive care unit stays, and comorbidities, nonelective hospitalizations were associated with acceleration in the rate of cognitive decline from before hospitalization, while elective hospitalizations were not. Nonelective hospitalizations were associated with an approximately 60% acceleration in the rate of decline.

“We saw a clear distinction: nonelective admissions drive the association between hospitalization and longterm changes in cognitive function in later life, while elective admissions do not necessarily carry the same risk of negative cognitive outcomes,” James said.

“These findings have important implications for the medical decision making and care of older adults. While recognizing that all medical procedures carry some degree of risk, this study implies that planned hospital encounters may not be as dangerous to the cognitive health of older persons as emergency or urgent situations.”

While the U.S. Congress has recently provided additional funding for Alzheimer’s research at the National Institutes of Health, the commitment continues to fall far short of the need. In 2017, for every $100 the NIH spends on Alzheimer’s research, Medicare and Medicaid will spend $12,500 caring for those with the disease. Congress must continue its commitment to Alzheimer’s and other dementias by increasing funding for Alzheimer’s research by at least an additional $414 million in fiscal year 2018.

About Alzheimer’s Association International Conference (AAIC)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2017 home page: www.alz.org/aaic/
AAIC 2017 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call +1 800.272.3900.

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  • Taylor Fields, et al. Self-Reported Hearing Loss, Cognitive Performance, and Risk of MCI: Findings from the Wisconsin Registry for Alzheimer’s Prevention. (Funder(s): University of Wisconsin at Madison Neuroscience Training Program)
  • Kimberly Mueller, Ph.D., et al. Signs of Early Cognitive Decline within Connected Speech: Evidence from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). (Funder(s): U.S. National Institutes of Health)
  • Bryan James, Ph.D., et al. Cognitive Decline after Elective and Nonelective Hospitalization in Community-Dwelling Older Adults. (Funder(s): National Institute on Aging)
Citation

http://alz.org/aaic/releases_2017/AAIC17-Mon-briefing-risk-factor.asp