Archives for September 2017

Prevention of Alzheimer’s Disease: Lessons Learned and Applied

2017 Aug 2. doi: 10.1111/jgs.14997. [Epub ahead of print]

Prevention of Alzheimer’s Disease: Lessons Learned and Applied.

Galvin JE1.


Alzheimer’s disease (AD) affects more than 5 million Americans, with substantial consequences for individuals with AD, families, and society in terms of morbidity, mortality, and healthcare costs. With disease-modifying treatment trials unsuccessful at the present time and only medications to treat symptoms available, an emerging approach is prevention. Advances in diagnostic criteria, biomarker development, and greater understanding of the biophysiological basis of AD make these initiatives feasible.

Ongoing pharmacological trials using anti-amyloid therapies are underway in sporadic and genetic forms of AD, although a large number of modifiable risk factors for AD have been identified in observational studies, many of which do not appear to exert effects through amyloid or tau. This suggests that prevention studies focusing on risk reduction and lifestyle modification may offer additional benefits. Rather than relying solely on large-sample, long-duration, randomized clinical trial designs, a precision medicine approach using N-of-1 trials may provide more-rapid information on whether personalized prevention plans can improve person-centered outcomes.

Because there appear to be multiple pathways to developing AD, there may also be multiple ways to prevent or delay the onset of AD. Even if these precision approaches alone are not successful in preventing AD, they may greatly improve the likelihood of amyloid- or tau-specific therapies to reach their endpoints by reducing comorbidities. Keeping this in mind, dementia may be a disorder that develops over a lifetime, with individualized ways to build a better brain as we age.

Alzheimer’s disease (AD) affects more than 5 million Americans, with substantial costs to individuals with AD, families, and society.[1] Projections by the Alzheimer Association are that, if nothing is done, by 2050, there will be more than 16 million people with AD in the United States and more than 60 million worldwide. Over the past 25 years, only five symptomatic medications have met their primary clinical trial endpoints in Phase III clinical trials and successfully come to market; of these, four are still available.

Since 2003, every symptom- and disease-modifying agent has failed in Phase II or III trials because of challenges with safety or efficacy. This led to a bold initiative put forth in the National Alzheimer Plan Act to develop a disease-modifying treatment (DMT) by 2025.[2] Two important concepts are associated with success to reach this target date. First, only medications that have already entered Phase II testing can make it to market by 2025.[2] Second, if a DMT were available by 2025, then the 2050 projection of 16 million Americans with AD would be reduced by 5.7 million cases, with societal savings of $367 billion.[1]

To complement efforts to develop a DMT for individuals with symptomatic AD, a concerted effort is underway to initiate preventive measures in asymptomatic individuals. Such efforts are also consistent with the 2025 target goal.An important question, is whether AD can be prevented. A large number of modifiable (e.g., exposures, lifestyle and social habits) and nonmodifiable (e.g., age, sex, genetics) risk factors have been identified (Table 1). Recent revisions to the clinical criteria for AD[3] and mild cognitive impairment (MCI)[4] helped clarify the role of biomarkers in defining the pathological cascade, and the addition of research criteria for presymptomatic disease[5] sets the stage for better modeling of the preclinical and prodromal stages of disease.[6]

Efforts developing and validating fluid (blood and cerebrospinal fluid) and imaging biomarkers make it possible to explore underlying pathological changes in amyloid, tau, dopamine transport, inflammation, signaling pathways, and in the future, alpha-synuclein and TDP-43 in symptomatic, prodromal, and presymptomatic individuals. Advances in genetic, epigenetic, and “omic” (e.g., proteomic, lipidomic, metabolomic) approaches will permit the modeling of transcriptional, translational, and posttranslational changes. Furthermore, precision medicine approaches with demonstrable benefits in oncology are being applied to neurodegenerative disorders. Thus, the platform is in place to begin prevention initiatives.

Table 1. Alzheimer’s Disease Risk and Protective Factors

  1. Apolipoprotein E is the major risk gene; a number of other minor risk genes have been identified.
Risk Factors (Nonmodifiable)
Family history
Apolipoprotein E ε4 allele*
Risk Factors (Modifiable)
Diabetes mellitus and insulin resistance
Metabolic syndrome
Cerebrovascular disease
Psychological and physiological stress
Traumatic brain injury
Sleep disordered breathing
Alcohol abuse
Protective Factors (Modifiable)
Cognitive reserve and mental activity
Educational attainment and lifelong learning
Cognitive leisure activities
Physical activity and exercise
Social engagement
Mindfulness and wellness activities
Optimism and purpose in life
Omega-3 intake


These efforts have a great potential for pharmaceutical and nonpharmacological approaches, with earlier identification of at-risk individuals, expanding opportunities for faster and earlier diagnoses, better stratification of at-risk individuals, higher enrollment into randomized clinical trials (RCTs) by reducing screen failure rates, and eventually more-effective treatments. Although the focus of this article is on AD, the principles discussed are relevant to related neurodegenerative disorders (e.g., Parkinson’s disease, Lewy body dementia, vascular dementia). Assuming that curing AD remains a substantial unsolved challenge, preventing or simply delaying the onset of dementia could significantly change the face of disease.

Pharmacological Approaches to Prevention

A number of prevention studies are ongoing in sporadic and autosomal-dominant forms of AD. Results are still pending, but a review of[7] provides important details about these studies. One such study is the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study, which is recruiting individuals aged 65 to 86 with normal cognitive function but positive AD biomarkers (amyloid deposition according to positron emission tomography). These individuals are followed for 3 years of treatment with an anti-amyloid monoclonal antibody. The Alzheimer Prevention Initiative will study individuals aged 60 to 75 with normal cognition who have two copies of the apolipoprotein E e4 allele, putting them at high risk of AD. These individuals are followed for 2 years of treatment with a different anti-amyloid monoclonal antibody. The TOMMORROW Study will enroll individuals aged 65 to 83 with normal cognition who have a polymorphism of the TOMM40 gene that is associated with greater risk of AD. Individuals are followed for 5 years of treatment with pioglitazone, an anti-diabetes drug. In parallel to these trials in sporadic cases with enhanced risk, trials are ongoing in individuals with autosomal-dominant forms of AD, including the Alzheimer Prevention Initiative and Dominantly Inherited Alzheimer Network—Treatment Unit using monoclonal antibodies. A particular advantage of the trials in familial AD is that age of onset is predictable so that, if a DMT effect exists, it is more likely to be detected. A potential disadvantage of these trials is that the results may not be generalizable to the much more common sporadic forms in which risk factors other than genetics may predominate.

Similar to prevention trials, there are number of prodromal studies with a major focus on individuals with MCI. Results are pending for many of these trials, but at least one Phase II study had promising results. Aducanumab immunotherapy[8] against the amyloid protein not only demonstrated changes in cerebrospinal fluid amyloid over 54 weeks in a dose-dependent manner, but also demonstrated significant changes in cognitive and functional measures. These findings support the concept that there may be a critical window for these agents to be administered to increase the likelihood of success.

Lifestyle Modification Interventions

Modifiable Lifestyle Factors

A number of modifiable risk and preventive factors for AD have been described in observational studies (Table 1). Risk factors that have been found in several studies include diabetes mellitus, hypertension, renal dysfunction, alcohol and smoking patterns, high cholesterol, coronary heart disease, depression, sedentary life style, low cognitive activity, and diet. These factors combined account for more than half of the attributable risk for AD.[9] The most difficult of these factors to address is diet because it is highly dependent on income and access to fresh foods.[10] In a 16-year observational study of 949 individuals using the Lifestyle for Brain Health (LIBRA) measure of modifiable risk factors, a 1-point increase in LIBRA score was associated with a 19% greater risk of dementia.[11] In a metaanalyses of 19 studies, cognitive leisure activities,[12] including crossword puzzles, card games, computer use, arts and crafts, life-long learning, group discussions, and music, had a protective effect (odds ratio (OR) = 0.58). In addition, physical activities may lead to a 20% to 65% risk reduction depending on the type and intensity of activity through mechanisms involving lower vascular disease risk, better respiratory function, stimulation of trophic factors, and lower oxidative stress and inflammation.[13] Objective measurement of midlife vascular risk factors demonstrated greater risk of dementia in late life.[14] In a study of 2,000 individuals aged 71 to 78, work-related stress increased the risk of MCI (OR = 1.38), dementia (OR = 1.53), and AD (OR = 1.55).[15]

Despite the differences between countries of origin, culture, language, educational attainment, and ages studied, the aforementioned studies and many others are convergent for a short list of risk factors that seem to play a critical role in the development or prevention of AD and related disorders. This consistency has led to the implementation of a number of dementia prevention initiatives to modify these risk factors, most of which cannot be directly linked to amyloid or tau deposition.

Ongoing Prevention Initiatives

The European Prevention of AD[16] initiative is recruiting participants to examine whether alteration of risk factors for AD that occur in early and mid-life potentiate pathophysiological changes decades before dementia onset. The Innovative Midlife Intervention for Dementia Deterrence trial[9] is examining 11 identified risk factors (e.g., diabetes, hypertension, renal) that account for half of the attributable risk and has enrolled 600 individuals to participate in an on-line education intervention. The largest initiative to date is the FINGER study,[17] enrolling 1,260 individuals in an educational intervention that includes modules in diet, exercise, cognitive training, and vascular risk reduction. Overall between-group differences were statistically significant for global cognition, executive function, and processing speed but not episodic memory.[17] These results suggest that lifestyle modification may offer some benefit in cognitive function, albeit with a small effect size.

Precision Medicine Approaches to Prevention

Although age is the single greatest risk factor for AD, AD is not inevitable. The best estimates suggest that, at age 85, there is 42% risk of developing AD,[1] which means that 58% of older adults do not develop dementia, even if amyloid can be detected in the brain. The reasons are unknown, but may be explained in part by a host of modifiable and nonmodifiable risk factors (Table 1). Up to 30% of AD cases may be preventable through modification of risk factors and behavioral changes to mitigate the effect of those risk factors that are not modifiable.[18] There is an ongoing debate as to whether the current evidence base is sufficient to initiate prevention programs because it is difficult to prove causation from observational studies, and it is difficult to pool multiple RCTs because of differences in study design, measurements used, and anticipated outcomes.[18] Although a well-balanced, healthy lifestyle may be the cornerstone of disease prevention and brain health, each risk factor (vascular, lifestyle choices, psychosocial) may both act independently and potentiate the effects of each other.[19, 20] Therefore, a prevention initiative needs to be multimodal and tailored to address individual risks.

These requirements lead to a number of design and analytical challenges. Many prevention RCTs use time-to-event analytical strategies to demonstrate a DMT effect. Such designs are optimal when anticipated treatment effects remain constant over time, but in the case of dementia prevention, this is unknown. Thus, time-to-event analyses such hazard ratios may not be the best way to model effects, particularly if the detectable signal is a late effect of the intervention.[21] Because AD is heterogeneous in terms of risk factors, age of onset, presentation, progression, and pathology burden, designing a study to treat individuals as a homogenous population requires large sample sizes (thousands to tens of thousands) to be followed for long periods of time (years to decades).[22] This results in large study costs, staff burden, and participant burden. In the absence of robust biomarkers that mark disease onset and progression, rather than just the presence of pathology, RCT design will remain a challenge.[23] Barriers to prevention studies include limited understanding of the real relationship between dementia risk factors and the effect of risk reduction; complexity of the effect of life course on dementia risk factors; lack of standardization of study design, definitions, and outcomes; difficulty translating RCT findings into real-world practice; cultural and social barriers to implementation; lack of research capacity to enroll large research cohorts for long periods of time; and pervasive social stigma associated with AD.[18]

Because effective prevention strategies are elusive despite significant advances in understanding of the biology and pathophysiology of AD, an alternative approach would be to take advantage of precision medicine designs used in oncology trials to tailor interventions to an individual’s phenotypic and genotypic expression. With better classification and phenotyping of individuals with AD, trial-ready cohorts can be targeted more appropriately with interventions (pharmacological and nonpharmacological) designed to ameliorate specific pathological mechanisms, based on specific biomarkers and individual characteristics.[23] Future trials could then be created to determine efficacy and safety (fast to fail) more quickly by moving away from one-size-fits-all approaches to person-specific precision treatments.

This would also require rethinking trial design for prevention measures, moving to more N-of-1 designs. N-of-1 trials consider the individual as the sole unit of observation to study the efficacy and adverse effects of an intervention[22] and are guided by objective data-driven criteria while leveraging the study designs and statistical techniques common to RCTs.[22] Because risk and molecular profiles of AD vary widely by person, grouping individuals into single entities (placebo vs treatment arm) may mix “super-responders” with “nonresponders,” washing out treatment effects that only become apparent in post hoc analyses.[24] Instead, comparing time-to-disease progression of an individual using a novel therapeutic approach to the time-to-disease progression for that same individuals for the immediately preceding treatment paradigm may be preferable.[25] N-of-1 trials may be less bound by threats to generalizability of large RCTs due to recruitment delays and challenges to translate significant p-values in large treatment groups to the care of an individual, which is the ultimate goal of clinical practice. In a metaanalyses of 70 N-of-1 trials, 50 of 57 completed trials provided definitive clinical or statistical answers, with 39% prompting physicians to change the plan of care.[26] Another metaanalysis examined 108 trials involving 2,154 participants and found that 54% of participants had subsequent treatment decisions changed based on the results.[27] To create the platform for such trials, several conditions must be met (Table 2). Participants must be deeply phenotyped with characterization of sociodemographic, psychological, clinical, cognitive, functional, biomarker, and genetic traits. Ideally, these individuals would agree to be followed longitudinally, have samples banked for future analyses, and consent to autopsy to provide confirmation of diagnosis and treatment effects on brain pathology. Statistical considerations may take advantage of alternative time-series analyses and within- and between-subject comparisons. Lastly, an important concern is the cost of care when a high-cost intervention is planned—for example, off-label treatment with an expensive medication.[22]

Table 2. Basic Principles of a Dementia Prevention Program

Establish a longitudinal cohort of individuals without memory impairment and with prodromal disease
Develop a protocol that can measure person-centered and health-economic outcomes
Evaluate clinical, cognitive, functional, and behavioral features annually
Collect and bank biomarkers: blood, spinal fluid, deoxyribonucleic acid, cell lines, magnetic resonance imaging, positron emission tomography
Encourage autopsy participation
Perform deep phenotyping of individuals with near total participation in all biomarker collection protocols by all participants
Apply precision medicine–type interventions to match treatment to individual characteristics
Test customized N-of-1 interventions over a designated period to determine whether protocols alter biophysiological profiles, disease-relevant biomarkers, and outcome measures
Develop a statistical plan to incorporate immediate, intermediate, and long-term time-to-event analyses
Create a trial-ready cohort for large-scale pharmacological and nonpharmacological interventions


Example of a Personalized Medicine Approach to Dementia Prevention

As an example of how this may applied in a pragmatic sense, N-of-1 trials are being developed to personalize dementia prevention using an evidence-base derived from an extensive literature review and results of a National Institutes of Health–funded project to conduct dementia screening in multicultural communities (R01 AG0402–11-A1, study design reviewed[28, 29]). In addition to screening for cognitive impairment, broader medical screening for diabetes mellitus, hypertension, vascular risk factors, obesity, mobility, physical performance, frailty, and depression was incorporated into a “healthy body, healthy mind” approach to make the concept of dementia screening more acceptable and to understand the effect of comorbid disease on cognitive performance. This cross-sectional study confirmed many findings of observational studies regarding the association between cognitive performance and diabetes mellitus, hypertension, obesity, vascular risk factors, and depression while providing novel findings linking cognitive performance to sarcopenia[28] and mobility.[29] These collective findings were prospectively applied to develop N-of-1 trials. For example, a 68-year-old college-educated woman (although an actual case, some features were altered to preserve anonymity) presented with a 1-year history of subjective memory complaints (misplacing car keys, forgetting conversations, defensiveness about memory issues) but with independent functioning in everyday activities. Her relevant past history was significant for hypertension and hypercholesterolemia. Physical examination findings included mild hypertension (blood pressure 132/92 mmHg) but normal cardiac and peripheral vascular examinations. Pertinent neurological findings included mild symmetric weakness, poor vibration sensation in the lower extremities, and mild postural instability. Cognitive testing revealed global deficits (Montreal Cognitive Assessment score 19/30), working memory and executive dysfunction, and episodic memory deficits on list learning that disappeared with cued recognition. Physical and functional testing revealed low lean muscle mass, at-risk nutritional status, modest daily physical activity, mild deficits in physical functionality (Short Physical Performance Battery score 7/12), and mild frailty (Fried Frailty Phenotype Score 3/5). Gait and balance testing revealed slowed gait speed (1.07 m/s), marked slowing (22.9%) with a dual-task challenge (walking while talking), and postural sway with eyes closed. Blood-based biomarkers revealed an abnormal lipid profile (high total, low-density lipoprotein (LDL), and non–high-density lipoprotein (HDL) cholesterol; high LDL and small LDL particles; and low HDL particles), high inflammatory markers (high-sensitivity C-reactive protein and myeloperoxidase), apolipoprotein (Apo)E 3/4 genotype, and evidence of insulin resistance (high fasting glucose, glycosylated hemoglobin, and estimated average glucose). Quantitative magnetic resonance imaging (MRI) revealed normal hippocampal size and lateral ventricle volume but confluent white matter hyperintensities with frontal lobe predominance. Auditory event–related potentials demonstrated slow median reaction times and low amplitude at the N200 peak (linked to impaired attention and executive function) and left–right asymmetry with frontal predominance (linked to vascular injury) but normal amplitudes and latencies at all other peaks, including the P50 peak associated with amyloid deposition.[30] This deep phenotypic evaluation provided findings in cognitive testing (executive and working memory deficits with cued episodic memory improvements supporting intact hippocampal circuitry), physical testing (sarcopenia, at-risk nutritional status, poor physical functionality, and early frailty), gait testing (slowed gait speed, impaired dual tasks, postural instability with eyes closed), biomarker testing (lipid profile, inflammation, insulin resistance, ApoE4 genotype suggesting poor response to statins), MRI (preservation of hippocampal and cortical volume, extensive white matter disease), and electroencephalography (executive dysfunction and evidence of vascular injury) that could be treated and supported a diagnosis of vascular cognitive impairment. A personalized treatment plan was then developed focusing on dietary counseling (Mediterranean-DASH Intervention for Neurodegenerative Delay diet, high-protein snacks, glycemic control); physical therapy for gait, balance, strengthening, and conditioning; referral to a personal trainer for aerobic, resistance, and flexibility training; mindfulness (yoga, meditation) for stress reduction; cognitive exercise focusing on problem-solving skills; omega-3 supplementation and possible resin therapy for cholesterol lowering; better blood pressure monitoring; and initiation of low-dose aspirin to improve blood flow. Longitudinal follow-up is needed to monitor adherence to recommendations and for evidence of improvement in outcomes. Such a trial could provide a direct estimate of individual treatment effects, fine-tune personalized care plans, enhance precision of future treatment decisions, improve person-centered outcomes, and if successful, reduce long-term healthcare costs.[25]


There is increasing evidence that multiple medical conditions increase the risk of neurodegeneration and subsequent development of dementia (Figure 1). It is also becoming clear that the majority of these risk factors act in amyloid- and tau-independent ways. Trials testing the amyloid hypothesis (β- and γ-secretase inhibitors, antiaggregation medications, mono- and polyclonal antibody approaches), antiinflammatory agents, and early-phase anti-tau therapies have failed to meet outcomes or have been discontinued because of safety concerns. While we wait for successful pharmacotherapy, these multiple pathways leading to AD can be taken advantage of to test hypotheses regarding risk reduction and mitigation. In all likelihood, efforts to prevent cognitive decline and development of dementia may be more successful when they are multimodal and directed to at-risk individuals based on their personal health profile, rather than using “one-size-fits-all” approaches. The detection of and interventions addressing root causes may offer novel approaches to diagnosing, treating, curing, or preventing AD. AD offers a large array of potentially modifiable risk factors (lifestyle, exposure, environment, comorbid disease) that are excellent targets to personalize the approach to medical care. Precision medicine approaches specifically target the heterogeneity of AD by identifying person-specific risk factors and applying a customized intervention directed against this risk profile. Even if these precision approaches do not cure or prevent AD, removing other pathways to neurodegeneration may greatly improve the likelihood that amyloid- or tau-specific therapies reach their endpoints. Perhaps it is time to abandon generalized approaches to AD and consider neurodegenerative disorders as diseases of a lifetime and that there may be individualized ways to build a better brain as we age.

Figure 1. Model of a dementia-prevention initiative. (A) Hypothetical model of the development of clinical dementia. Before diagnosis, there would be evidence of cognitive decline, which reflects neurodegenerative changes including cellular dysfunction and loss, synaptic dysfunction, and loss of connectivity. Presumably, accumulation of one or more pathologies cause these downstream changes. If more than one pathology is present, each should have its own risk factor or factors (e.g., Risk Factor A causes Pathology A, Risk Factor B causes Pathology B). (B) Application of model in N-of-1 trial (described in detail in text). Six risk factors were identified during the clinical evaluation, presumably working through different pathways, with the end result being neurodegeneration, cognitive decline, and if unchecked, eventually clinical dementia. A personalized prevention plan directed at root causes of impairment, if successful, would prevent the conversion of cognitive decline to dementia (marked by X). Because root causes may interact or potentiate each other’s effect on neurodegeneration (connecting arrows on the left side), multimodal approaches are more likely to have an effect than single approaches.




Conflict of Interest: Dr. Galvin serves as a scientific advisor for Axovant, Biogen, Eisai, and Eli Lilly; receives licensing fees from Pfizer, Lilly, Axovant, and Quintiles; and conducts on-going clinical trials funded by Biogen, Axovant, and Janssen. Dr. Galvin is funded by grants from NIH (R01 AG0402–11-A1, U01 NS100610, and R01 NS088040–01), the Florida Department of Health, the Harry T. Mangurian Foundation, and the Association for Frontotemporal Degeneration. He is on the editorial boards of Neurodegenerative Disease Management, Alzheimer’s Disease and Associated Disorders, and Acta Neuropathologica.

Author Contributions: Dr. Galvin was responsible for the study design, statistical analyses and interpretation, drafting, and revising and submitting the manuscript.

Sponsor’s Role: None.

© 2017, Copyright the Author Journal compilation © 2017, The American Geriatrics Society.


Thinking ‘Out-Of-The-Box’ May Build a Better Brain and Prevent Dementia

(Florida Atlantic University) More than 5 million Americans today are affected by Alzheimer’s disease (AD). If nothing is done to stop this upward trajectory, there will be more than 16 million people with AD in the United States and more than 60 million people with AD worldwide by 2050. In the past 25 years, only five symptomatic medications for AD have met their primary clinical endpoints in Phase III clinical trials and successfully come to market; of these, four are still available.

There is increasing evidence that multiple medical conditions increase the risk of neurodegeneration and subsequent development of dementia. It also is becoming clear that a majority of those risk factors acts in amyloid- and tau-independent ways. Since 2003, every symptom- and disease-modifying agent has failed in Phase II or III trials because of challenges with safety or efficacy, including trials testing the amyloid hypothesis, anti-inflammatory agents, and early-phase anti-tau therapies.

With disease-modifying treatment trials unsuccessful at the present time and only medications to treat symptoms available, what now?

Thinking “out-of-the-box,” a leading neuroscientist at Florida Atlantic University has developed an innovative program in the Comprehensive Center for Brain Health at FAU called the “Dementia Prevention Initiative” (DPI), which abandons generalized methods used to research and treat AD. His secret weapon: a novel “N-of-1 design” that individualizes medicine down to a single patient. Instead of conducting a conventional trial of 100 people all getting the same treatment, he has switched it around and is conducting 100 single trials personalized to the individual. His youngest patient is 61 and the oldest is 86.

“Because Alzheimer’s disease is heterogeneous in terms of risk factors, age of onset, presentation, progression, and pathology burden, designing a study to treat individuals as a homogenous population requires thousands of patients who have to be followed for years and even decades. This approach is very costly and burdensome on clinicians and patients,”

said James E. Galvin, M.D., M.P.H., associate dean for clinical research in FAU’s Charles E. Schmidt College of Medicine, a world-renowned neuroscientist, a leading international expert on AD and Lewy Body Dementia (LBD), and founder of the DPI.

The DPI is a two-year clinical trial and Galvin is developing a best-practice model of personalized care that looks at each individual as the sole unit of observation. The idea is to treat neurodegenerative diseases as a disorder that develops over a lifetime and individualize ways to build a better brain as we age. The ultimate goal is to prevent dementia from happening in the first place.

Galvin’s approach follows a form of personalized treatment similarly used in cancer and delivers an individualized prevention plan, tailored to each patient’s risk profile based on their genetic traits, biomarkers (blood, imaging, and electrophysiology), socio-demographics, lifestyle choices, and co-existent medical conditions.

This approach specifically targets the heterogeneity of AD by identifying person-specific risk factors and applying a customized intervention directed against this risk profile. Galvin anticipates that this method will provide more rapid information on whether personalized prevention plans can improve person-centered outcomes.

“While we know that a well-balanced, healthy lifestyle may be the cornerstone of disease prevention and brain health, each risk factor such as vascular, lifestyle choices, psychosocial behavior may both act independently and potentiate the effects of each other. Therefore, a prevention initiative needs to be multimodal and tailored to address individual risks,” said Galvin.

Although the single greatest risk factor for AD is age, AD is not inevitable. It is estimated that at age 85 there is a 42 percent risk of developing AD, which means that 58 percent of older adults do not develop dementia, even if amyloid can be detected in the brain. The reasons are unknown, but may be explained in part by a host of modifiable and non-modifiable risk factors. Up to 30 percent of AD cases may be preventable through modification of risk factors and behavioral changes to mitigate the effect of those risk factors that can’t be modified.

FAU Neuroscientist James Galvin, M.D., uses the functional range of motion board to test a patient’s manual dexterity as part of the Dementia Prevention Initiative program he developed. image is credited to Florida Atlantic University.

“We know what’s good for the heart is good for the brain and we are changing people’s blood profiles, controlling blood sugars, reducing inflammation, lowering blood pressure, and changing lipids and cholesterol,” said Galvin.

“Our patients say that they are in better overall health, their moods have improved and they are more physically fit than before.”

Even if these precision approaches alone are not successful in preventing AD, Galvin believes that they may greatly improve the likelihood of amyloid- or tau-specific therapies reaching their endpoints by reducing comorbidities.

“Prevention of Alzheimer’s Disease: Lessons Learned and Applied,” was recently published in the Journal of the American Geriatrics Society.

Nationally, if the onset of AD and related disorders is delayed by five years, 25 years later there would be approximately 5.7 million fewer cases, collective family savings would approach $87 billion, and societal savings would approach $367 billion.


Funding: The study was funded by the Harry T. Mangurian, Jr. Foundation.

Source: Gisele Galoustian – Florida Atlantic University

Original Research: Full open access research for “Prevention of Alzheimer’s Disease: Lessons Learned and Applied” by James E. Galvin MD, MPH in Journal of American Geriatrics Society. Published online August 2 2017 doi:10.1111/jgs.14997


Both High, Low Levels of Magnesium in Blood Linked to Risk of Dementia

(American Academy of Neurology) People with both high and low levels of magnesium in their blood may have a greater risk of developing dementia, according to a study published in the September 20, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“These results need to be confirmed with additional studies, but the results are intriguing,” said study author Brenda C.T. Kieboom, MD, MSc, of Erasmus University Medical Center in Rotterdam, the Netherlands. ”

Since the current treatment and prevention options for dementia are limited, we urgently need to identify new risk factors for dementia that could potentially be adjusted. If people could reduce their risk for dementia through diet or supplements, that could be very beneficial.”

The study involved 9,569 people with an average age of 65 who did not have dementia whose blood was tested for magnesium levels. The participants were followed for an average of eight years. During that time, 823 people were diagnosed with dementia. Of those, 662 people had Alzheimer’s disease.

The participants were divided into five groups based on their magnesium levels. Both those with the highest and the lowest levels of magnesium had an increased risk of dementia, compared to those in the middle group.

Both the low and high groups were about 30 percent more likely to develop dementia than those in the middle group. Of the 1,771 people in the low magnesium group, 160 people developed dementia, which is a rate of 10.2 per 1,000 person-years. For the high magnesium group, 179 of the 1,748 people developed dementia, for a rate of 11.4 per 1,000 person-years. For the middle group, 102 of the 1,387 people developed dementia, for a rate of 7.8.

The results were the same after researchers adjusted for other factors that could affect the risk of dementia and magnesium levels, such as body mass index, smoking status, alcohol use and kidney function.

Kieboom noted that almost all of the participants had magnesium levels in the normal range, with only 108 people with levels below normal and two people with levels above normal.

Foods that are good sources of magnesium include spinach, almonds, cashews, soy and black beans, whole grains, yogurt and avocados.

Kieboom said that if the results are confirmed, blood tests to measure magnesium levels could be used to screen for people at risk of dementia. She emphasized that the study does not prove that high or low levels of magnesium cause dementia; it only shows an association.

Limitations of the study include that magnesium levels were measured only once, so they could have changed, and that magnesium levels in the blood do not always represent the total level of magnesium in the body.


Journal Reference:

Brenda C.T. Kieboom, Silvan Licher, Frank J. Wolters, M. Kamran Ikram, Ewout J. Hoorn, Robert Zietse, Bruno H. Stricker, M. Arfan Ikram. Serum magnesium is associated with the risk of dementia. Neurology, 2017; 10.1212/WNL.0000000000004517 DOI: 10.1212/WNL.0000000000004517
Copyright 2017 ScienceDaily or by other parties, where indicated.


Alzheimer’s Disease: When Does Personality Start to Change?

(MedicalNewsToday) A new study recently published in the journal JAMA Psychiatry investigates whether or not changes in personality precede the onset of mild cognitive impairment or dementia.

The researchers – who were jointly led by Antonio Terracciano and Angelina Sutin, both associate professors at Florida State University College of Medicine in Tallahassee – investigated dementia-related personality changes in a cohort of more than 2,000 people.

The longitudinal study followed these participants for 36 years, during which time the researchers looked for increased neuroticism, decreased conscientiousness, and other personality changes.

It is known that personality and behavioral changes accompany Alzheimer’s disease. Caregivers report irritability, moodiness, or loss of motivation in their patients, which negatively affect their quality of life.

These are clinical criteria for diagnosing the illness, but it remains debatable whether or not these changes occur before the onset of dementia – as a consequence of the brain pathologies that characterize the disease and occur years before a formal diagnosis – or whether personality changes are just independent risk factors for the condition.

Personality Stays the Same Before Onset

For the new study, 2,046 participants were recruited from the Baltimore Longitudinal Study of Aging. Of them, 45.5 percent were female, and the average age was 62 years.

During the follow-up period, little over 5 percent of the participants developed mild cognitive impairment (MCI) and 12.5 percent developed dementia. The majority of these patients had Alzheimer’s disease.

MCI describes a level of cognitive decline that affects seniors. Although it is not serious enough to interfere with the daily functioning of those it affects, MCI is considered to be a strong predictor of Alzheimer’s disease.

Prof. Terracciano and colleagues used the Revised NEO Personality Inventory to assess changes in personality traits, as they were observed and reported by the participants themselves.

The questionnaire assessed five different personality dimensions: “neuroticism, extraversion, openness, agreeableness, and conscientiousness.”

The researchers examined the “slopes” that depicted personality changes over time, and they compared the trajectories of those who went on to develop dementia or MCI with those of cognitively healthy participants.

Having adjusted for age, sex, race, and education, the researchers found that “change in personality […] was not significantly different between the non-impaired and the Alzheimer’s disease group.”

When compared with healthy individuals, participants who developed MCI did not exhibit any personality changes, either.

In other words, the study found that the personalities of people with Alzheimer’s disease remain unchanged before the onset of the condition.

We further found that personality remained stable even within the last few years before the onset of mild cognitive impairment.”

Prof. Antonio Terracciano

Additionally, the study adds to the evidence showing that certain personality traits, such as high levels of neuroticism, can increase the risk of dementia.

The authors write that these results “provide evidence against the reverse causality hypothesis.” This hypothesis refers to the possibility that changes in personality are a consequence of Alzheimer’s neuropathology, such as the build-up of amyloid plaque in the brain.

But the findings strengthen the idea that certain personality traits associated with Alzheimer’s disease are, in fact, independent risk factors for the condition, rather than a consequence of it.

Strengths and Limitations of the Study

Speaking about the study’s strengths, Prof. Terracciano says,

“Unlike previous research, this study examined multiple waves of self-rated personality data collected up to 36 years before participants developed any sign of dementia.”

In addition to the long-term follow-up, the authors list the considerable sample size and the “in-depth personality and clinical assessments” as strengths of the study.

However, they also admit some limitations to their research. For one thing, the sample was limited to people with a higher level of education.

Also, participants who did not develop dementia during the follow-up tended to be younger on average, so the authors concede that these people may go on to develop dementia in the future.

Finally, the authors note that some personality traits might make some people resilient to the brain pathology that characterizes Alzheimer’s disease. More research is warranted in this direction.


By Ana Sandoiu

Healthline Media UK Ltd, Brighton, UK.

© 2004-2017 All rights reserved.


Personality Change in the Preclinical Phase of Alzheimer Disease

JAMA Psychiatry. Published online September 20, 2017. doi:10.1001/jamapsychiatry.2017.2816

Personality Change in the Preclinical Phase of Alzheimer Disease

Antonio Terracciano, PhD1,2; Yang An, MS2; Angelina R. Sutin, PhD1,2; et al

Key Points

Question  Do changes in personality traits occur before the onset of mild cognitive impairment or clinical dementia?

Findings  In a cohort study that followed up 2046 older adults for as long as 36 years, no evidence of significant change in self-rated personality was found before the onset of mild cognitive impairment or clinical dementia.

Meaning  No personality changes that could be characterized as an early sign of dementia were found.


Importance  Changes in behavior and personality are 1 criterion for the diagnosis of dementia. It is unclear, however, whether such changes begin before the clinical onset of the disease.

Objective  To determine whether increases in neuroticism, declines in conscientiousness, and changes in other personality traits occur before the onset of mild cognitive impairment or dementia.

Design, Setting, and Participants  A cohort of 2046 community-dwelling older adults who volunteered to participate in the Baltimore Longitudinal Study of Aging were included. The study examined personality and clinical assessments obtained between 1980 and July 13, 2016, from participants with no cognitive impairment at first assessment who were followed up for as long as 36 years (mean [SD], 12.05 [9.54] years). The self-report personality scales were not considered during consensus diagnostic conferences.

Main Outcomes and Measures  Change in self-rated personality traits assessed in the preclinical phase of Alzheimer disease and other dementias with the Revised NEO Personality Inventory, a 240-item questionnaire that assesses 30 facets, 6 for each of the 5 major dimensions: neuroticism, extraversion, openness, agreeableness, and conscientiousness.

Results  Of the 2046 participants, 931 [45.5%] were women; mean (SD) age at first assessment was 62.56 (14.63) years. During 24 569 person-years, mild cognitive impairment was diagnosed in 104 (5.1%) individuals, and all-cause dementia was diagnosed in 255 (12.5%) participants, including 194 (9.5%) with Alzheimer disease.

Multilevel modeling that accounted for age, sex, race, and educational level found significant differences on the intercept of several traits: individuals who developed dementia scored higher on neuroticism (β = 2.83; 95% CI, 1.44 to 4.22; P < .001) and lower on conscientiousness (β = −3.34; 95% CI, −4.93 to −1.75; P < .001) and extraversion (β = −1.74; 95% CI, −3.23 to −0.25; P = .02).

Change in personality (ie, slope), however, was not significantly different between the nonimpaired and the Alzheimer disease groups (eg, neuroticism: β = 0.00; 95% CI, −0.08 to 0.08; P = .91; conscientiousness: β = −0.06; 95% CI, −0.16 to 0.04; P = .24).

Slopes for individuals who developed mild cognitive impairment (eg, neuroticism: β = 0.00; 95% CI, −0.12 to 0.12; P = .98; conscientiousness: β = −0.09; 95% CI, −0.23 to 0.05; P = .18) and all-cause dementia (eg, neuroticism: β = 0.02; 95% CI, −0.06 to 0.10; P = .49; conscientiousness: β = −0.08; 95% CI, −0.16 to 0.00; P = .07) were also similar to those for nonimpaired participants.

Conclusions and Relevance  No evidence for preclinical change in personality before the onset of mild cognitive impairment or dementia was identified. These findings provide evidence against the reverse causality hypothesis and strengthen evidence for personality traits as a risk factor for dementia.


© 2017 American Medical Association.


Dancing May Help to Combat Brain Aging

(MedicalNewsToday) Get your dancing shoes on – your brain will thank you for it. This is the take-away message from a new study, which found that physical activity in later life – particularly dancing – can help to reverse the signs of brain aging.

As we age, a number of brain changes occur, including a decrease in brain tissue, a reduction in blood flow, and a decline in communication between brain cells.

All of these changes can interfere with cognitive functioning, especially learning and memory.

Previous studies have suggested that physical activity in later life can help to reduce cognitive decline. A study reported by Medical News Today last year, for example, linked regular moderate- to high-intensity exercise to a slower decline in memory and thinking skills for the over-50s.

But which forms of exercise are most effective against brain aging? Lead study author Dr. Kathrin Rehfeld, of the German center for Neurodegenerative Diseases in Germany, and colleagues sought to answer this question with their new research.

They recently reported their findings in the journal Frontiers in Human Neuroscience.

Dancing and the Hippocampus

The study included 52 healthy adults aged 63-80 years. Each participant was randomly assigned to one of two exercise groups for 18 months.

One group was required to participate in a 90-minute dancing lesson each week for 18 months, while the other group engaged in 90 minutes of strength-endurance training each week.

The researchers note that physical activity varied between each group; while the dance group faced new routines every week, the activities of the strength-endurance training group were repetitive.

“We tried to provide our seniors in the dance group with constantly changing dance routines of different genres (Jazz, Square, Latin-American and Line Dance),” says Dr. Rehfeld.

“Steps, arm-patterns, formations, speed and rhythms were changed every second week to keep them in a constant learning process,” she adds. “The most challenging aspect for them was to recall the routines under the pressure of time and without any cues from the instructor.”

At study baseline and at the end of the 18-month exercise interventions, each participant underwent magnetic resonance imaging (MRI) of the brain. Additionally, subjects’ balance before and after intervention was evaluated using the Sensory Organization Test.

The researchers found that both groups demonstrated an increase in hippocampal volume, but dancers showed the greatest increase.

The hippocampus is the brain region associated with learning, memory, and emotion, and it is the region commonly affected by age-related brain changes.

Interestingly, however, only dancers showed an increase in neuronal connections in the dentate gyrus of the hippocampus, which is an area associated with memory formation.

Improved Balance for Dancers

Notably, the team found that dancing also led to significant improvements in participants’ balance, while the strength-endurance training group experienced no such benefit.

Dr. Rehfeld and team speculate that the continuous learning process involved in dancing might explain the additional benefits observed.

“The dancers showed increases in some HC [hippocampus] subfields where there was no change to be observed in the sports group. This indicates that apart from physical fitness, other factors inherent in dancing contribute to HC volume changes, too,” write the authors.

“We […] can conclude that the additional challenges involved in our dance program, namely cognitive and sensorimotor stimulation, induced extra HC volume changes in addition to those attributable to physical fitness alone,” they add.

The team notes that the relationship between dancing, fitness training, and brain aging should be further investigated in larger studies. In particular, the researchers believe future research should assess whether dancing might help to prevent or delay Alzheimer’s disease and other neurodegenerative disorders.

In the meantime, the researchers recommend that older adults get up and move their feet to a beat – it could do wonders for the brain.

“I believe that everybody would like to live an independent and healthy life, for as long as possible. Physical activity is one of the lifestyle factors that can contribute to this, counteracting several risk factors and slowing down age-related decline,” says Dr. Rehfeld.

I think dancing is a powerful tool to set new challenges for body and mind, especially in older age.”


By Honor Whitman

Healthline Media UK Ltd, Brighton, UK.

© 2004-2017 All rights reserved.


Alzheimer’s Grief, Loss, and Bereavement

(Alzheimer’s Society) Friends, family and other people close to a person with dementia may experience feelings of grief, and similar emotions related to loss and bereavement. These feelings can occur from the point of diagnosis through to the person’s death, and beyond. They may even occur before the diagnosis, as symptoms start to develop.

People with dementia may experience grief at the point of diagnosis, and while living with the condition. They may also experience grief when bereaved by the death of someone close to them.

This factsheet is for carers, friends and relatives of people with dementia. It looks at some of the feelings carers may experience and suggests ways to cope. It also looks at supporting a person with dementia to cope with grief and bereavement.


Grief is a normal response to a significant loss, but can become a complex psychological and emotional experience. It is common for someone who cares for a person with dementia to experience grief. This can occur while they are caring for the person and after the person has died.

Carers may experience grief as the person’s dementia progresses and increasingly affects their relationship with the person. They may grieve for the losses they and the person with dementia experience. Some carers may feel in a continual state of grieving.

The type of grief a carer may experience can depend on a range of factors such as their relation to the person (eg spouse, partner, sibling, child or friend), the type of dementia the person has, and the stage of dementia.

Grief can be difficult to detect as it can be shown in many different ways, including:

  • helplessness/despair
  • withdrawal
  • anger/frustration
  • guilt
  • denial
  • not acknowledging losses
  • longing for what has been lost
  • sadness
  • acceptance.

It is important to acknowledge feelings of grief when they occur. It is a complicated and highly individual experience – there is no right or wrong way to grieve. Carers may find that it changes over time.

People with dementia may also experience grief as their condition progresses. They may grieve for the loss of abilities, skills and independence. They may develop a sense of isolation as their environment becomes more unfamiliar and confusing. They may be frightened about what the future holds.

Anticipatory Grief

People with dementia and carers sometimes experience grief in anticipation of the losses the condition may cause. This is known as anticipatory grief. For carers this can happen throughout the course of dementia, and a person in the early or middle stages of the condition may experience it too. Some evidence suggests that carers who experience anticipatory grief may cope better with the grief they experience after bereavement, though this grief may still be painful. Sometimes experiencing anticipatory grief may also increase the possibility of a carer becoming depressed. It can help for carers to discuss their feelings while they are still caring for the person with dementia.


People can experience strong feelings associated with loss when a person close to them develops dementia. It can sometimes be more difficult to manage these feelings than it is to cope with practical aspects of caring. Depending on the carer’s relationship with the person, and their individual circumstances, they may experience the loss of:

  • their relationship
  • intimacy
  • companionship, support and special understanding from the person
  • communication between themselves and the person
  • shared activities and hobbies
  • freedom to work or pursue other activities
  • a particular lifestyle
  • a planned future
  • previous relationship roles.

Loss and grief can play a part in someone’s ability to cope with caring. Some losses, such as the loss of meaningful, interpersonal relationships with the person with dementia, can result in grief that may be more difficult to manage than the person’s actual death.

As dementia progresses, a relationship may move from one that was mutually supportive to one where the carer takes on more responsibility. The person with dementia may become increasingly dependent on their support. This can be very difficult to adjust to.

It’s important that carers seek support for emotions associated with loss. Family members, friends or professionals (eg a dementia support worker) could provide this. Attending support groups with other carers, or accessing an online forum (such as Alzheimer’s Society’s Talking Point) can be good ways to seek support and information.

It can be difficult for a carer to manage these feelings if others don’t see the feelings as significant, or don’t appreciate or understand them. Those around the carer may be in denial or not fully understand the impact dementia has. This can lead to a lack of support for the carer.

Ambiguous Loss

Some carers also struggle with a more psychological sense of loss in the relationship (also known as ambiguous or unclear loss). The personality of the person with dementia is seen as lost or considerably changed, but they are physically still present. Ambiguous loss may result in feelings of unresolved grief, and can also stop people from accessing help and support.


It is normal for someone caring for a person with dementia to experience feelings of grief. They may cope well at some times, and at other times feel overwhelmed by sadness or anger, or may simply feel numb. They may feel resentful at how things have turned out and the difficulties they have to face. Some people may be shocked to find that they feel this resentment. It’s important to know that caring for a person with dementia can have a huge emotional impact, and feelings like these can be a normal part of grieving. Anyone experiencing such feelings may be under a great deal of stress, and may need to seek some emotional support.

Dealing with Emotions: Tips for Carers

  • Try not to bottle up your emotions: talk about your feelings. This may be with aprofessional (eg a dementia nurse), other carers (eg via a support group), a friend or family member.
  • Try to make time for yourself each day. This could be relaxing, walking outside, a hand massage or chatting to friends.
  • Consider your own needs. If you feel that you need a break to help you cope, speak to someone about arranging this.
  • Try to focus on the positives, for example things that you and the person with dementia can still do together, or other interests you have.
  • If you’re feeling low or anxious, or are very tired or not sleeping, speak to your GP. It’s important to look after your own physical and mental health.

Residential Care

When a person with dementia goes into residential care, their carer may experience a range of conflicting emotions, including relief, sadness and guilt. They may be worried about how the person will settle in, and whether the care they receive will be good enough. A move into residential care is a big change in the caring relationship, and the carer may miss the person’s presence. They may also feel that they are no longer able to play an active part in the person’s care. All of this may contribute to increased feelings of guilt and sadness.

If someone has been a carer for a long time, the move to residential care can have a profound impact on their role. They may feel lost and have a sense of emptiness, and it can be emotionally draining. Other people may expect a carer to be able to re-establish their life quickly after the person goes into care and may not appreciate how emotionally difficult the situation is. Someone who has been caring for a parent may find it easier to re-establish their life than someone who has been caring for a spouse.

There may also be practical and financial issues to consider when the person goes into care (eg living arrangements) which can affect a carer’s feelings and ability to cope.

Moving to residential care: tips for carers

  • You don’t stop being a carer just because you no longer do the practical day-to-day tasks.
  • If you still want to be involved in caring for the person, speak to the care home staff and discuss how you can work together.
  • You will know the person’s likes, dislikes, hobbies, routines, life history and more. All of this can help care home staff to support the person.
  • Initially, you may want to take some time away from caring altogether. The care home should support you with this and welcome you back when you’re ready.
  • Though you may want to visit the person in their new home, try not to build your life around this. You need to take care of yourself and your needs.
  • Consider attending a support group: the care home may have a group for relatives and carers. These can help you to talk through your feelings about the changes you’re experiencing.
  • You will experience your own feelings in your own way. It is important to know that there is no right or wrong way to feel.


Bereavement at the death of a friend or relative with dementia is a unique and complex situation that everyone will cope with in their own way. It is a normal experience and many people won’t need professional support. A carer’s reaction to the death may depend on many factors, including:

  • their relationship with the person
  • their personal situation
  • the stage of the person’s dementia
  • responses to losses that have already happened over the course of caring for the person
  • the circumstances surrounding the person’s death.

It may feel like the final loss of many, and can also represent a turning point in the carer’s life.

Carers may experience a range of emotions during bereavement, both positive and negative. Emotional reactions to bereavement may include:

  • sadness
  • shock and pain (even if the death has been expected for a while)
  • anger and resentment about what has happened
  • guilt about how the person was cared for
  • numbness, as though feelings are frozen
  • inability to accept the situation
  • feelings of isolation
  • a feeling of lack of purpose
  • relief, both for the person with dementia and for themselves.

Sometimes when a person dies, the carer may not be in a position to fully experience grief, and it can take a long time for feelings to come out. This is called delayed grief. It may happen because:

  • it takes a while to accept the person has died
  • the feelings are overwhelming and suppressed at the time
  • the carer must sort out the person’s affairs and therefore doesn’t have time to grieve.

Delayed grief may especially happen if the carer has cared for the person for a long time.

Carers may find they have a sense of emptiness after bereavement. They may struggle to come to terms with the loss of the person, loss of their defined role, excess free time (loss of past interests and hobbies may make this difficult to fill), and not being in touch with previous relationships because of the time spent as a carer. All of this can add to feelings of loneliness. Some people find it hard to adjust to living without the person with dementia. It can help for them to talk through these feelings with someone they trust.

Some carers may find it helpful to meet with professionals who were involved with the care of the person with dementia at least once after bereavement.

It’s important for carers to be supported to express and explore their emotions after bereavement.

When the Person Dies: Tips for Carers

  • Try to avoid making any major decisions in the early months if you’re still feeling shocked or vulnerable.
  • Take some time to reflect and come to terms with your situation, but try not to isolate yourself.
  • It’s not unusual to think you have heard the person’s voice or seen the person after they have died and while you’re grieving.
  • Keeping hold of items that the person treasured or that remind you of them (such as a watch or a favourite scarf) may help you to keep a sense of connection.
  • Even though you may generally be coping, there may be times when you feel particularly sad or upset.
  • If you find events such as anniversaries or birthdays upsetting, ask for support from friends or family.
  • Stay in touch with your GP. You may be more vulnerable to physical illness, as well as anxiety, stress and depression after bereavement.
  • If you feel your grief is becoming overwhelming, seek bereavement support services.

Readjusting after Bereavement

Life does not return to being the same after bereavement. However, the time will come when the pain eases and a carer feels ready to cope with life without the person who died. Some carers find getting back on their feet easier than others. It takes time to adjust, and how long it takes will vary from person to person. If someone is struggling and time doesn’t seem to be helping, they may want to think about professional support.

Readjusting: Tips for Carers

  • Talk about the person who died, and reminisce about them and the life you shared.
  • Try to eat properly and get enough rest (even if you don’t manage to sleep).
  • Allow yourself space and time to grieve.
  • Take things slowly and ask for help and support, if you need it. Tell people what you need: if you don’t, they may not know how to help.
  • Try to get socially involved and re-establish past interests and hobbies, or consider starting new ones.

If you’re concerned about forgetting the person, there are some things you can do that may help:

  • Talk about the person and your memories of them.
  • Create a photo album.
  • Keep some of their personal belongings.
  • Do something to commemorate them, such as planting a tree or arranging a memorial gathering for those close to the person.

Supporting a Person with Dementia During Bereavement

People with dementia will experience bereavement in a range of ways and their needs will be similar to those of someone who doesn’t have dementia. However, the person’s cognitive difficulties may create unique challenges.

Telling the Person About a Death

When someone close to a person with dementia dies, it raises the question of whether or not to tell them. There may also be the question of how much detail to tell them, especially if the circumstances of the death could cause the person distress. These are difficult situations and there is no one solution that will work for everyone. It will depend on the individual, their situation and what is in their best interests. Whatever decision is made, it’s very important to acknowledge and support the person’s emotional responses.

If the person is not told about the death it may prevent the grieving process and leave them feeling afraid and unsupported when, for example, the person who has died appears to have stopped visiting without explanation. However, telling the person may lead to unnecessary distress and they may be unable to process the information.

Talking over the situation with professionals may help. Whatever is decided, it’s important for the person to be supported as much as possible.

Telling the Person About a Death: Tips for Carers

  • Provide information clearly, simply and without euphemisms (eg ‘passed away’).
  • Use body language and physical contact if appropriate.
  • Try not to give too much information at once.
  • Allow plenty of time for the conversation and be supportive.
  • Be prepared to repeat information.
  • If the person becomes very distressed, try a different approach.
  • Make sure that you are supported as well.

Like anyone, a person with dementia may respond to bereavement in a range of ways. However, how they understand information and adapt to the bereavement may be complicated by problems with thinking and reasoning. However, just because someone has dementia, it doesn’t mean they are unable to feel emotions at the bereavement and experience grief.

The dementia may also interfere with a person’s usual means of coping, so it’s important for them to feel safe and supported. It can also disturb someone’s ability to accept the death, and to vocalise any distress and emotions they’re feeling.

There are many ways that a person with dementia may respond to the death of someone close to them:

  • They may come up with an alternative reason for why the person is no longer around, for example that they’re at work or on holiday. This may be caused by denial, poor memory or confabulation (filling in gaps with things the person believes to be true), or a combination of these things.
  • They may mistake others for the person who has died, eg a son for a husband. This can be caused by memory loss and/or problems recognising people.
  • Changes in the brain mean they may have difficulty regulating emotional responses and may express their grief in different ways such as through theirbehaviour. They may become attached to one possession, eg a coat or an ornament, and not want to be parted from it, or they may refuse to take part in an activity they enjoy, eg singing.

Supporting the Person to Grieve

It may be difficult to know whether a person with dementia is grieving. If they are grieving it’s important to support them to do so. Being involved in conversations and arrangements after the death (eg the funeral) may help the person with dementia take in the loss and start the grieving process. However, if the person appears not to be grieving, it may be best to let them be.

If someone starts to behave in challenging ways, it may be a direct reaction to the bereavement, or a sign of distress that they are not being supported to grieve. It can help for carers to observe the person and see if there are things triggering or maintaining a grief response. Identifying these may help a carer to support the person to grieve, or help them find a way to avoid triggers.

Supporting the Person to Grieve: Tips for Carers

  • Acknowledge feelings and encourage the person to express themselves.
  • Reminiscence can be helpful after a bereavement.
  • Allow the person with dementia to talk/communicate about the person who has died.
  • Giving the person something that reminds them of the person who died may help with feelings of connectedness and can be used to support reminiscence, if appropriate.
  • Consider creative outlets such as art and music. These can help support people to express their feelings and grief.
  • Consider other ways to meet the person’s attachment needs, such as comfort objects, spiritual means and other relationships.
  • The person may find comfort in their spiritual beliefs such as prayer, meditation or faith practices.

If the person’s main carer dies it can lead to lots of upheaval and change in the person’s life. They are likely to need lots of support, guidance and assistance to adjust to these changes.

When a person with dementia experiences a bereavement they sometimes experience and remember a profound shock and sense of bewilderment. At other times they may not recall or understand the loss, but it can still have a strong emotional impact on them, reflected in their behaviour and mood.

Asking for the Person Who Has Died

A person with dementia may forget that someone has died. They may ask about them repeatedly, come up with reasons for their absence (such as being away or having left them), or report them as missing. This can be very difficult for family and friends coming to terms with the death, as well as the person with dementia. If they are told again that the person has died, it may be like hearing it for the first time. How a carer should respond will depend on the individual and what is in their best interests.

Reminding a Person with Eementia of a Death: Tips for Carers

  • For some people, a gentle reminder that the person has died may help. For others this will be very upsetting.
  • Reminders of the funeral, shown and discussed in a supportive way, may help the person to absorb the news. Personal possessions may also help.
  • Recognising and focusing on the person’s emotional state can make knowing what to say easier.
  • If the person is in the later stages of dementia, trying to remind them that the person has died is unlikely to work and may be very distressing.
  • If someone is becoming very upset it may be best not to try and remind them.
  • Support the person through changes in emotion and behaviour. Reminiscence and other creative techniques (eg art or music) can be helpful for this.
  • Look for patterns to when the person is asking. If there is one (eg at 5pm they always had a cup of tea together) you may be able to put techniques in place to help. For example, at 5pm ask the person about hobbies they used to do together to encourage positive reminiscence.
  • Be patient, responsive and aware that adjusting to the loss will take time.

If responding to the emotion or reminiscence doesn’t work, you could try distraction. However, while this may alleviate the stress of the moment, it may not help the grief process in the long term.

Past Bereavements

A person with dementia may forget about a past bereavement, and hear of it as if for the first time. It can feel as though it’s just happened, and they may experience the emotions all over again. They may struggle to process the information that the death happened a long time ago, and be left with the feeling of a recent bereavement. They may also confuse a present loss with a previous one (eg husband with father).

Supporting a person with dementia who is bereaved can present many challenges. However, there are things carers, family and friends can do to help the person feel safe and supported. It is also important for carers, family and friends to address their own needs and feelings of grief during loss and bereavement.


Factsheet 507

All content © 2017 Alzheimer’s Society.

How to Get Your Prescription Drugs During a Disaster

(AARP) Thousands of people rescued from rooftops and plucked from rising water during Hurricane Harvey had to leave everything behind. For many, prescription drugs were among the items they abandoned. The same may happen to those fleeing Hurricane Irma.

Missing days of essential medicine can pose a health threat and adds to the sense of panic people feel during such emergencies — especially natural disasters. Fortunately, disaster response teams and medical units have been set up across the ravaged Texas counties. Those teams are helping provide access to prescription refills and vital medical care.

“This is a horrible, devastating time, but people should realize that continuing to take their medicines will help them meet the challenges,” said Barbara Young of the American Society of Health-System Pharmacists.

For example, the more than 10,000 evacuees taking shelter at the George R. Brown Convention Center in Houston have an on-site medical facility — established by the U.S. Department of Health and Human Services. Additional medical stations have opened in Dallas.

Texas state law allows pharmacists to dispense as much as a 30-day supply of a prescription drug during a natural disaster without a doctor’s authorization. American Red Cross volunteers also are authorized to help with refilling prescriptions in an emergency.

Even for people who were able to gather their medicines before evacuating their homes, there’s a concern about drugs that require refrigeration. It’s important to check with medical experts or a pharmacist for advice. Any drugs that have been exposed to flood water or unsafe tap water should be discarded, as they might be contaminated.

Government and charitable organizations have some tips for individuals and their families who require medicine or need places to receive treatments, such as drug infusions and kidney dialysis. Here is a sampling of available resources.

  • To find an open pharmacy, go to, which maps open and closed pharmacies during disasters. The site also has locations of American Red Cross shelters and infusion centers in the affected communities.
  • Low-income patients can go to community health centers or clinics where the charity Direct Relief ( provides free prescription drugs and medical supplies. Direct Relief has already pre-positioned medical supplies at 14 locations across Florida.
  • For those with a Medicare Prescription Drug Plan, recommends contacting the plan to find the nearest network pharmacy that is open. If one is unavailable, the plan can connect evacuees with an out-of-network pharmacy. People might have to pay full price, but may be eligible for a refund. Call your plan for more details and instructions. To find your plan’s phone number, call 1-800-MEDICARE.
  • Medicare recipients who need dialysis treatments should contact their End-Stage Renal Disease Network (ESRD) or call 800-MEDICARE to get ESRD Network contact information. Those who have a Medicare Advantage Plan should contact their provider to find out how they can get supplies, transportation to dialysis services and other information about dialysis treatments.
  • For people who need chemotherapy or other cancer treatments, the National Cancer Institute (800-4CANCER) can help locate cancer care providers.

Copyright 2017 AARP