Is it Alzheimer’s Disease or Dementia with Lewy Bodies?

(BrightFocus Foundation) The most common cause of Major Neurocognitive Disorder (the new term for what physicians had previously called dementia) is Alzheimer’s disease (AD); only about one third of older adults with dementia have a different condition.

How Common is Lewy Body Dementia?

After AD, Lewy body dementia (LBD) or dementia with Lewy bodies is one of the most frequent causes of dementia, affecting some 1.3 million Americans. To put this in perspective, Alzheimer’s affects about four times as many older adults. LBD usually can begin between ages 50 and 85, and typically becomes clinically apparent during a person’s mid-to-late 70s. The disease usually runs its course over about 6 years.

What are Lewy Bodies?

The microscopic findings in brain tissue from LBD patients are different from those in people with AD. The important distinction is that in LBD there are small “Lewy bodies” inside the brain’s cells. These Lewy bodies are neither plaques nor tangles, but rather synuclein, the same protein found in brains of people with Parkinson’s disease. The clinical disease of LBD reflects the widespread distribution of Lewy bodies, which are especially dense in parts of the brain most specialized for movements, memories, reasoning, and emotions.

nftLewy Body


Similar to people with AD, those affected by LBD develop cognitive difficulties that can include problems with memory and reasoning. Executive function and visuospatial cognition are prominently affected as well. Social and occupational functioning are affected to such a degree that ultimately the patient must depend on others for basic care. Unlike AD, the LBD patient shows symptoms that resemble Parkinson’s disease: muscle stiffness, rigidity, and tremor.

Other characteristics that differentiate LBD from AD include disturbances of autonomic function, resulting in changes in blood pressure, temperature, and digestion; fluctuation of cognitive status so that there are very good days and very bad days; fainting and falling; and intense visual hallucinations. Depressed mood, too, is common among those affected by LBD, and may represent not only a psychological reaction to this devastating disease but also a neurochemical consequence of its pathology.

In some cases, the onset of LBD is preceded by a remarkable and potentially dangerous disturbance of sleep called REM Behavior Disorder (RBD). Unlike people who sleep normally and whose muscles remain quiet during dreams, those with RBD can act out their dreams because their muscles remain active like those of an awake person. This activity can have dangerous, even life-threatening consequences, when an affected person strikes a bed partner or hurls himself out of bed while still asleep. This sleep disorder is not characteristic of AD.


LBD, as you can see, can produce some severe behavioral changes. In people with AD, behavioral symptoms that threaten a person’s safety or the safety of others, may be treated with antipsychotic medications (although this is controversial and only one of the available options). Perhaps because LBD shares pathological and clinical features with not only AD but also Parkinson’s disease, physicians see a response to these antipsychotic medications in LBD that is toxic and even dangerous, similar to the reaction that a person with Parkinson’s disease might have to antipsychotic medications. The person with LBD who receives even a small dose of an antipsychotic medication can become profoundly stiff, sedated, and more confused and agitated. Other medications, such as serotonergic antidepressants, have a better chance of helping these patients’ non-cognitive symptoms.

Special Concerns for the Caregivers

Caregivers of patients with LBD are stressed in many of the same ways as caregivers of AD patients. The cognitive decline, decreasing functional capacity, and non-cognitive disturbances are every bit as stressful. In addition, though, LBD patients can present special concerns because their ability to function changes from day to day. Their falls and hallucinations add further stress and risk. Their response to cognitive enhancers such as the cholinesterase inhibitors or memantine can be as good as that of AD patients, so their use should be considered.

A Clear Diagnosis is Important

Cost-conscious observers of health care point out that our treatments for Major Neurocognitive Disorders are limited in their scope and only modestly effective. Knowing the cause of a cognitive disorders will be of greatest value, they point out, once we have very specific treatment approaches for different diseases. In the case of LBD, knowing the diagnosis is of great value, because it may alert clinicians to the potentially hazardous effects of a class of medications often used to treat behavioral disturbances in AD. For this reason, even if for no others, identifying LBD is already a very worthwhile endeavor. In time, diagnostic clarity should become even more valuable as future treatments are developed to target LBD specifically.

More Information

A specialized source of information and support is the LBD Association, and their online caregiver community is available through their website. Finally, the National Institute on Aging provides helpful information on LBD for patients, families and caregivers.



Human Brain Deficits of PKCe: Targeted for Alzheimer’s Disease Therapeutic and Diagnostic Trials

(IOS Press) Today, researchers at the Blanchette Rockefeller Neurosciences Institute (BRNI) announced findings from a new study entitled, “PKCe Deficits in Alzheimer’s Disease Brains and Skin Fibroblasts.”

These new findings offer significant promise for a new therapeutic and diagnostic approach to Alzheimer’s disease (AD) that has remained so refractory to effective and early drug treatment. This approach is now the major focus of ongoing clinical trials being conducted by at BRNI/Neurotrope, Inc. collaboration.

In contrast to past strategies, this new therapeutic strategy now being clinically tested, not only removes the precursors to amyloid plaques and tangles, it also induces the growth of new synapses and prevents neuronal death.

The results of this study, co-authored by Tapan K. Khan, Ph.D.; Abhik Sen, Ph.D.; Jarin Hongpaisan, Ph.D.; Chol S. Lim, Ph.D.; Thomas J. Nelson, Ph.D.; and Daniel L. Alkon, M.D. can be found in an early online edition of the Journal of Alzheimer’s Disease.

In this study, brain samples, provided under blinded conditions by the Harvard Brain Bank, PKC epsilon were found to be deficient in areas of the brain known to be affected early in AD.

In these same brain areas, this new report also shows that the A Beta oligomers levels rise when PKC epsilon is reduced. The study also compared the skin cells of AD patients with age-matched controls and patients with non-AD dementias. This comparison found consistent changes in the skin cells of AD patients.

Thus, these PKC epsilon deficits in the brain support their potential value both as an early therapeutic target in AD, and as an early diagnostic biomarker in skin cells that are easily obtained in a minimally invasive sample.

BRNI, in collaboration with its private sector partner, Neurotrope, Inc. recently launched clinical trials of a drug, Bryostatin, that activates PKC epsilon now discovered to be deficient in AD brains – as well as in skin fibroblasts.  This enzyme, PKC epsilon, not only regulates the formation and degradation of the AD toxic proteins, A Beta oligomers, it also reduces the precursor to another AD hallmark, neurofibrillary tangles.

This same enzyme, PKC epsilon, stimulates the formation of new synaptic connections that are lost even early in AD. PKC epsilon activation by this highly potent BRNI/Therapeutic, Bryostatin, also stimulates pathways to prevent the death of neurons.

Importantly, the PKC epsilon deficits in the skin cells were strongly correlated with disease progression.   The longer the patients had AD, the greater the PKC epsilon deficits. Furthermore, the deficits in the brain were significantly correlated with an accepted measure of disease severity known as the “Braak” score.

“The results of this study demonstrates strong evidence that a peripheral Alzheimer’s biomarker in skin cells, even early in the disease progression, provides a direct window into the the Alzheimer’s brain which show PKC epsilon deficits that could account for the early loss of synaptic connections and dementia,” says Dr. Alkon, Scientific Director of the Blanchette Rockefeller Neurosciences Institute, and Chief Scientific Officer of Neurotrope, Inc.


PKCε Deficits in Alzheimer’s Disease Brains and Skin Fibroblasts, Tapan K. Khan, Abhik Sen, Jarin Hongpaisan, Chol S. Lim, Thomas J. Nelson, Daniel L. Alkon, Journal of Alzheimer’s Disease, Pre-Press (August 2014), DOI 10.3233/JAD-141221.

About the Blanchette Rockefeller Neurosciences Institute

The Blanchette Rockefeller Neurosciences Institute (BRNI) is a unique, independent, non-profit institute dedicated to the study of memory and finding solutions to memory disorders. BRNI was founded in 1999 in memory of Blanchette Ferry Hooker Rockefeller, an Alzheimer’s patient and mother of U. S. Senator John D. Rockefeller IV. BRNI is operated in alliance with West Virginia University as well as in collaboration with other academic institutions.

About Neurotrope

Neurotrope was formed in October 2012 principally to license, develop and commercialize various novel therapeutic and diagnostic technologies from BRNI. Neurotrope’s pipeline, under its license from BRNI, includes the drug candidate, bryostatin, for the treatment of Alzheimer’s disease; a minimally invasive, diagnostic biomarker analysis system which would assess the presence of Alzheimer’s in patients. A Phase 2a study with bryostatin in the treatment of Alzheimer’s disease is currently underway. In addition, Neurotrope has a world-wide, exclusive license agreement with the Icahn School of Medicine at Mount Sinai to utilize its proprietary information and data package for the use of Bryostatin-1 in the treatment of Niemann-Pick Type C Disease, a rare disease, mostly of children who are afflicted with Alzheimer-like symptoms. Also, as part of its license from BRNI, the Company, under its BRNI license, the rights to pursue treatments for a number of orphan diseases, including Fragile X Syndrome. The Company’s preclinical and clinical efforts are focused on the development of conventional small molecules that are extraordinarily potent in the activation of the enzyme PKCe, which has been shown to play a central role in the regrowth or repair of nervous tissues, cells or cell products.

About Bryostatin

Bryostatin is a natural product produced by a marine invertebrate organism called Bugula neritina and is isolated from organic matter harvested from the ocean. Several variations of this complex product have been achieved in recent years in various academic chemistry laboratories, including bryostatin derivatives being developed through an exclusive license with Stanford University and the existing license agreement with BRNI. These approaches may represent alternative sources of drug supply.



Creating Pomegranate Drug to Stem Alzheimer’s, Parkinson’s

(University of Huddersfield) Dr Olumayokun Olajide’s research will now look to produce compound derivatives of punicalagin for a drug that would treat neuro-inflammation.

08-olajide-main1Regular intake and regular consumption of pomegranate has many health benefits including prevention of neuro-inflammation related to dementia which slows down the progression of the disease.

The onset of Alzheimer’s disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate. Also, the painful inflammation that accompanies illnesses such as rheumatoid arthritis and Parkinson’s disease could be reduced, according to the findings of a two-year project headed by University of Huddersfield scientist Dr Olumayokun Olajide, who specialises in the anti-inflammatory properties of natural products.

Now, a new phase of research can explore the development of drugs that will stem the development of dementias such as Alzheimer’s, which affects some 800,000 people in the UK, with 163,000 new cases a year being diagnosed. Globally, there are at least 44.4 million dementia sufferers, with the numbers expected to soar.

The key breakthrough by Dr Olajide and his co-researchers is to demonstrate that punicalagin, which is a polyphenol – a form of chemical compound – found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as micrologia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer’s sufferers progressively worse.

There is still no cure for the disease, but the punicalagin in pomegranate could prevent it or slow down its development.

08-olajide-main3Dr Olajide worked with co-researchers – including four PhD students – in the University of Huddersfield’s Department of Pharmacy (pictured left) and with scientists at the University of Freiburg in Germany. The team used brain cells isolated from rats in order to test their findings.

Now the research is published in the latest edition of the journal Molecular Nutrition & Food Research and Dr Olajide will start to disseminate his findings at academic conferences.

He is still working on the amounts of pomegranate that are required, in order to be effective.

“But we do know that regular intake and regular consumption of pomegranate has a lot of health benefits – including prevention of neuro-inflammation related to dementia,” he says, recommending juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin, the compound that slows down the progression of dementia.

Dr Olajide states that most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. And he adds that although this has yet to be scientifically evaluated, pomegranate will be useful in any condition for which inflammation – not just neuro-inflammation – is a factor, such as rheumatoid arthritis, Parkinson’s and cancer.

The research continues and now Dr Olajide is collaborating with his University of Huddersfield colleague, the organic chemist Dr Karl Hemming. They will attempt to produce compound derivatives of punicalagin that could the basis of new, orally administered drugs that would treat neuro-inflammation.

Dr Olajide has been a Senior Lecturer at the University of Huddersfield for four years. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.

He attributes this area of research to his upbringing.

“African mothers normally treat sick children with natural substances such as herbs. My mum certainly used a lot of those substances. And then I went on to study pharmacology!”

The article “Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia”, by A. Olumayokun A. Olajide, Asit Kumar, Ravikanth Velagapudi, Uchechukwu P. Okorji and Bernd L. Fiebich is published by Molecular Nutrition & Food Research.



Alzheimer’s Disease: rAAV/ABAD-DP-6His Attenuates Oxidative Stress Induced Injury of PC12 Cells

(Neural Regeneration Research) The effects of Amyloid beta (Aβ)-Aβ-binding alcohol dehydrogenase (ABAD) may exacerbate Alzheimer’s disease pathology. Therefore, blocking Aβ-ABAD-mediate effects with ABAD decoy peptide (ABAD-DP) may be a potential therapeutic strategy for Alzheimer’s disease.

Dr. Jiang Wu and team from the First Hospital of Jilin University in China successfully constructed a recombinant adenovirus constitutively secreting and expressing Aβ-ABAD decoy peptide (rAAV/ABAD-DP-6His). Their results showed that rAAV/ABAD-DP-6His increased superoxide dismutase activity in hydrogen peroxide-induced oxidative stress-mediated injury of PC12 cells.

changes-in-morphologyProtective effect of rAAV/ABAD-DP on H2O2-mediated changes in morphology of PC12 cells. ABAD: Aβ-binding alcohol dehydrogenase; DP: decoy peptide; rAAV: recombinant adeno-associated viral vector; 6His: 6-His protein. Credit: Neural Regeneration Research

Moreover, rAAV/ABADDP-6His decreased malondialdehyde content, intracellular Ca2+ concentration, and the level of reactive oxygen species. rAAV/ABAD-DP-6His maintained the stability of the mitochondrial membrane potential.

In addition, the ATP level remained constant, and apoptosis was reduced.

Overall, the experimental findings, published in the Neural Regeneration Research, indicate that rAAV/ABAD-DP-6His generates the fusion peptide, Aβ-ABAD decoy peptide, which effectively protects PC12 cells from oxidative stress injury induced by hydrogen peroxide, thus exerting neuroprotective effects.


Article: ” rAAV/ABAD-DP-6His attenuates oxidative stress-induced injury of PC12 cells,” by Mingyue Jia1, Mingyu Wang2, Yi Yang1, Yixin Chen3, Dujuan Liu4, Xu Wang1, Lei Song1, Jiang Wu1, Yu Yang1 (1 Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, China; 2 Department of Neurology, People’s Hospital of Jilin Province, Changchun, Jilin Province, China; 3 Radioactive Medicine Specialty, College of Public Health in Jilin University, Changchun, Jilin Province, China; 4 Department of Burn and Plastic Surgery, the General Hospital of CNPC in Jilin, Jilin, Jilin Province, China)

Jia MY, Wang MY, Yang Y, Chen YX, Liu DJ, Wang X, Song L, Wu J, Yang Y. rAAV/ABAD-DP-6His attenuates oxidative stress-induced injury of PC12 cells. Neural Regen Res. 2014;9(5):481-488.



Pesticide Exposure Linked to Alzheimer’s Disease

(Fisher Center for Alzheimer’s Research Foundation) Exposure to the pesticide DDT may raise the risk of Alzheimer’s disease years later, a new study suggests. The finding raises concerns about the effects of environmental toxins on the brain and how they may affect the onset or severity of Alzheimer’s disease.

Though DDT has been banned in the United States since 1972, it was widely used beginning in the 1940s and residues can remain in the environment for decades. Many older adults were directly exposed to the chemical when young. DDT is also still used in many countries around the world for insect control in crops and livestock and to limit the spread of diseases like malaria, and it may be ingested in imported fruits, vegetables, fish and other foods.

For the study, scientists looked at DDE, the chemical that remains after DDT is broken down. They studied blood samples from 86 elderly men and women – average age 74 – with Alzheimer’s disease, and compared them with 79 of their healthy peers.

The researchers, from Rutgers University, Emory University and the University of Texas Southwestern Medical Center, found that 80 percent of those with Alzheimer’s had DDE residues in their blood. In comparison, only 70 percent of those without Alzheimer’s had DDE in their bodies. DDE levels in those with Alzheimer’s were, on average, almost four times higher than in those without the disease. The findings appeared in JAMA Neurology.

In the study, those who carried the APOE-E4 gene, which raises the risk of developing Alzheimer’s in old age, appeared to be particularly vulnerable to the possible effects of DDT. Those APOE-E4 carriers who had high levels of DDE in their systems showed greater declines in thinking and memory skills than similar patients without the gene. It is possible that DDT exposure may nudge people toward Alzheimer’s in those who are already genetically predisposed, the authors say.

In an editorial that accompanied the study, doctors noted that the results are preliminary and need further corroboration. But they say that it raises intriguing questions about the role of environmental factors in Alzheimer’s onset.

They point out that identical twins, for example, who share the same genes, typically do not get Alzheimer’s at the same rate or at the same age of onset. So factors besides genes likely play a role. Head injuries are a well known risk factor for Alzheimer’s, and other conditions like high cholesterol, diabetes, high blood pressure and obesity are linked to increased risk. While a study like this one shows a correlation between DDT exposure and Alzheimer’s, it cannot prove that pesticides actually cause the disease.

Pesticides have been strongly tied to other brain disorders, including Parkinson’s disease. The authors note that more research must be done to understand better the potential link between pesticides and Alzheimer’s.

“This study demonstrates that there are additional contributors to Alzheimer’s disease that must be examined and that may help identify those at risk of developing Alzheimer’s,” said the study leader, Dr. Jason Richardson, of the Department of Environmental and Occupational Medicine at Robert Wood Johnson Medical School at Rutgers. “It is important because when it comes to diagnosing and treating this and other neurodegenerative diseases, the earlier someone is diagnosed, the more options there may be available.”

By, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.



Dementia Risk Quadrupled in People with Mild Cognitive Impairment

(Journal of Alzheimer’s Disease) In a long-term, large-scale population-based study of individuals aged 55 years or older in the general population researchers found that those diagnosed with mild cognitive impairment (MCI) had a four-fold increased risk of developing dementia or Alzheimer’s disease (AD) compared to cognitively healthy individuals.

Several risk factors including older age, positive APOE-ɛ4 status, low total cholesterol levels, and stroke, as well as specific MRI findings were associated with an increased risk of developing MCI. The results are published in a supplement to the Journal of Alzheimer’s Disease.

“Mild cognitive impairment has been identified as the transitional stage between normal aging and dementia,” comments M. Arfan Ikram, MD, PhD, a neuroepidemiologist at Erasmus MC University Medical Center (Rotterdam). “Identifying persons at a higher risk of dementia could postpone or even prevent dementia by timely targeting modifiable risk factors.”

Unlike a clinical trial, the Rotterdam study is an observational cohort study focusing on the general population, instead of persons referred to a memory clinic. The Rotterdam study began in 1990, when almost 8,000 inhabitants of Rotterdam aged 55 years or older agreed to participate in the study. Ten years later, another 3,000 individuals were added. Participants undergo home interviews and examinations every four years.

“This important prospective study adds to the accumulating evidence that strokes, presumably related to so called ‘vascular’ risk factors, also contribute to the appearance of dementia in Alzheimer’s disease. This leads to the conclusion that starting at midlife people should minimize those risk factors.

The recent results of the Finish FINGER study corroborate this idea. It should be remembered that delaying the onset of dementia by five years will reduce the prevalence of the disease by half. And of course, since there is no cure for AD, prevention is the best approach at present,” explains Professor Emeritus Amos D Korczyn, Tel Aviv University, Ramat Aviv, Israel, and Guest Editor of the Supplement.

To be diagnosed with MCI in the study, individuals were required to meet three criteria: a self-reported awareness of having problems with memory or everyday functioning; deficits detected on a battery of cognitive tests; and no evidence of dementia. They were categorized into those with memory problems (amnestic MCI) and those with normal memory (non-amnestic MCI).

Of 4,198 persons found to be eligible for the study, almost 10% were diagnosed with MCI. Of these, 163 had amnestic MCI and 254 had non-amnestic MCI.

The risk of dementia was especially high for people with amnestic MCI. Similar results were observed regarding the risk for Alzheimer’s disease. Those with MCI also faced a somewhat higher risk of death.

The research team investigated possible determinants of MCI, considering factors such as age, APOE-ɛ status, waist circumference, hypertension, diabetes mellitus, total and HDL-cholesterol levels, smoking, and stroke. Only older age, being an APOE-ɛ4 carrier, low total cholesterol levels, and stroke at baseline were associated with developing MCI. Having the APOE-ɛ4 genotype and smoking were related only to amnestic MCI.

When the investigators analysed MRI studies of the brain, they found that participants with MCI, particularly those with non-amnestic MCI, had larger white matter lesion volumes and worse microstructural integrity of normal-appearing white matter compared to controls.

They were also three-times more likely than controls to have lacunes (3 to 15 mm cerebrospinal fluid (CSF)-filled cavities in the basal ganglia or white matter, frequently observed when imaging older people).  MCI was not associated with total brain volume, hippocampal volume, or cerebral microbleeds.

“Our results suggest that accumulating vascular damage plays a role in both amnestic and non-amnestic MCI,” says Dr. Ikram. “We propose that timely targeting of modifiable vascular risk factors might contribute to the prevention of MCI and dementia.”



Lifestyle Changes May Lengthen Telomeres, A Measure of Cell Aging

(University of California San Francisco) A small pilot study shows for the first time that changes in diet, exercise, stress management and social support may result in longer telomeres, the parts of chromosomes that affect aging. It is the first controlled trial to show that any intervention might lengthen telomeres over time. The study was published online on Sept. 16, 2013 in The Lancet Oncology.

The study was conducted by scientists at UC San Francisco and the Preventive Medicine Research Institute, a nonprofit public research institute in Sausalito, Calif. that investigates the effect of diet and lifestyle choices on health and disease. The researchers say they hope the results will inspire larger trials to test the validity of the findings.

“Our genes, and our telomeres, are not necessarily our fate,” said lead author Dean Ornish, MD, UCSF clinical professor of medicine, and founder and president of the Preventive Medicine Research Institute.

“So often people think ‘Oh, I have bad genes, there’s nothing I can do about it,’” Ornish said. “But these findings indicate that telomeres may lengthen to the degree that people change how they live. Research indicates that longer telomeres are associated with fewer illnesses and longer life.”

Study of Early-Stage Prostate Cancer Patients

Telomeres are the protective caps on the ends of chromosomes that affect how quickly cells age. They are combinations of DNA and protein that protect the ends of chromosomes and help them remain stable. As they become shorter, and as their structural integrity weakens, the cells age and die quicker.

In recent years, shorter telomeres have become associated with a broad range of aging-related diseases, including many forms of cancer, stroke, vascular dementia, cardiovascular disease, obesity, osteoporosis and diabetes.

Life Style Changes_graphic_v2For five years, the researchers followed 35 men with localized, early-stage prostate cancer to explore the relationship between comprehensive lifestyle changes, and telomere length and telomerase activity. All the men were engaged in active surveillance, which involves closely monitoring a patient’s condition through screening and biopsies.

Ten of the patients embarked on lifestyle changes that included: a plant-based diet (high in fruits, vegetables and unrefined grains, and low in fat and refined carbohydrates); moderate exercise (walking 30 minutes a day, six days a week); stress reduction (gentle yoga-based stretching, breathing, meditation). They also participated in weekly group support.

They were compared to the other 25 study participants who were not asked to make major lifestyle changes.

The group that made the lifestyle changes experienced a “significant” increase in telomere length of approximately 10 percent. Further, the more people changed their behavior by adhering to the recommended lifestyle program, the more dramatic their improvements in telomere length, the scientists learned.

By contrast, the men in the control group who were not asked to alter their lifestyle had measurably shorter telomeres – nearly 3 percent shorter – when the five-year study ended. Telomere length usually decreases over time.

Possibilities for General Population

The researchers say the findings may not be limited to men with prostate cancer, and are likely to be relevant to the general population.

“We looked at telomeres in the participants’ blood, not their prostate tissue,” said Ornish.

The new study is a follow up to a similar, three-month pilot investigation in 2008 in which the same participants were asked to follow the same lifestyle program. After three months, the men in the initial study exhibited significantly increased telomerase activity. Telomerase is an enzyme that repairs and lengthens telomeres.

The new study was designed to determine if the lifestyle changes would affect telomere length and telomerase activity in these men over a longer time period.

“This was a breakthrough finding that needs to be confirmed by larger studies,” said co-senior author Peter R. Carroll, MD, MPH, professor and chair of the UCSF Department of Urology.

“Telomere shortening increases the risk of a wide variety of chronic diseases,” Carroll said. “We believe that increases in telomere length may help to prevent these conditions and perhaps even lengthen lifespan.”



Physical Activity and Alzheimer’s-related Hippocampal Atrophy

(National Institute of Aging) Physical activity may help prevent atrophy of the hippocampus, a brain region important for learning and memory that often shrinks in the brains of people with Alzheimer’s disease. A recent study that looked at the rate of atrophy over 18 months in cognitively normal older adults suggests that physical activity may help prevent or delay this Alzheimer’s-related change.

The NIA-funded study by researchers at the Cleveland Clinic’s Schey Center for Cognitive Neuroimaging is the first to show the protective effects physical activity may have on the hippocampus in older adults at genetic risk for Alzheimer’s. It also adds to past findings that physical activity, from gardening to walking to structured exercise programs, may benefit cognitive function in older adults.

Researchers studied 97 cognitively normal adults, age 65 to 89, some of whom had a family history of dementia. They were divided into four groups based on their self-reported levels of physical activity (low or high) and the presence or absence of the apolipoprotein E (APOE) ɛ4 gene form, the strongest known genetic risk factor for Alzheimer’s disease. Individuals with low physical activity said they walked or did other low-intensity activities on 2 or fewer days per week; those with high activity said they engaged in moderate or vigorous activity, such as brisk walking or swimming, on 3 or more days per week.

All participants underwent magnetic resonance imaging (MRI) of the brain to measure the size of the hippocampus—a part of the brain that shrinks as Alzheimer’s progresses—and other brain structures, as well as neurobehavioral testing to measure cognition and daily functioning. MRI scans were done at the beginning of the study and after 18 months.

At the study end, researchers found the size of the hippocampus decreased by 3 percent in the group with high genetic risk and low physical activity. Hippocampal size remained stable in the group with low genetic risk and in participants with high genetic risk/high physical activity. Physical activity did not appear to affect several other brain areas, including the amygdala, thalamus, and cortical white matter.

While promising, more research is needed to confirm these findings. Researchers want to learn how physical activity influences hippocampal atrophy in people at high genetic risk of Alzheimer’s. Animal studies suggest several possibilities, including the impact of physical activity on cholinergic function, brain inflammation, and cerebral blood flow.