Dr. Claudia Satizabal[/caption]
Claudia L. Satizabal, PhD
Instructor in Neurology
Boston University School of Medicine
The Framingham Heart Study
Boston, MA 02118-2526
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Satizabal: Our societies are expected to face an increasing burden of dementia in the next decades due to increasing life expectancies and the aging of a big proportion of the population, the so called “baby boomers”. However, some studies conducted in high-income countries have suggested a decline in the total number of cases (prevalence) as well as new cases (incidence) of dementia at any given age. Yet the findings of these studies were not seen as definitive, either because results were of borderline significance or because they were based on survey data, and stronger evidence was lacking.
We used information collected since 1975 in the Framingham Heart Study to estimate the trends in dementia incidence. One of the strengths of this study is that investigators have been careful to use the same diagnostic criteria for over the past 30 decades, which allows us to provide more robust evidence of dementia trends over time.
We found that there has been a progressive decline in the incidence of dementia at any given age over the past 30 decades. Compared to the late 1970s, we observed a decline of 22% in the late 1980s, 38% in the 1990s and 44% in the 2000s. This beneficial trend was only seen among persons with at least a high school diploma. We also explored trends in vascular risk factors such as blood pressure, smoking, diabetes, and others; however, these trends did not completely explain the decline in dementia incidence. One interesting finding was that the risk of dementia associated with cardiovascular diseases, such as stroke or atrial fibrillation, decreased dramatically over the course of time from the late 1970s to the 2000s.
Dr. Kelley[/caption]
MedicalResearch.com Interview with:
Amy S. Kelley, MD, MSHS
Department of Geriatrics and Palliative Medicine
Icahn School of Medicine at Mount Sinai
New York, NY
Medical Research: Why is it so important to understand the financial burdens families may face in providing end-of-life care for a loved one and why do you think the burdens may be greater for dementia than for other medical conditions?
Dr. Kelley: Understanding the financial risks that older adults face in the last years of life is important for individuals and families, in order to plan and save, if possible. It is also important for our policy makers, in particular, to know about these costs so that this information can help shape health and social policy that will best serve our society. Households of those with dementia face the greatest burden of costs, on average, particularly with regard to out-of-pocket expenses and the costs of caregiving. Many costs related to daily care for patients with dementia are not covered by health insurance, and these care needs, including everything from supervision, to bathing and feeding, may span several years.
MedicalResearch.com Interview with:
Christine McGarrigle PhD
Research Director
The Irish Longitudinal Study on Ageing (TILDA)
Lincoln Gate
Trinity College Dublin Dublin
Medical Research: What is the background for this study? What are the main findings?
Dr. McGarrigle: Mild cognitive impairment (MCI) is the intermediate state between healthy ageing and dementia and is a stage at which intervention could be effective in reducing conversion to dementia.
Neurocardiovascular instability is an age-related dysregulation of the blood pressure systems manifesting as exaggerated blood pressure variability and orthostatic hypotension (OH). Previous evidence has shown that autonomic dysfunction, blood pressure variation and hypotension are associated with mild cognitive impairment.
Our study found that systolic blood pressure variation was associated with cognitive decline. Mild cognitive impairment participants were more likely to have had OH and more prolonged OH compared to cognitively normal controls. Mild cognitive impairment participants with impaired orthostatic blood pressure responses were twice more likely to convert to dementia than mild cognitive impairment participants without the impaired response over a three year follow-up period.
MedicalResearch.com Interview with:
Meera Sheffrin MD
Geriatrics Fellow
Division of Geriatrics | Department of Medicine
San Francisco VA Medical Center
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Sheffrin: The main drug treatments for dementia are a class of medications called cholinesterase inhibitors. They have only modest effects on cognition and function in most patients, but since they are one of the few available treatments for dementia and thus very commonly prescribed. However,they are known to cause GI side effects (nausea, vomiting, diarrhea, and anorexia) in many patients when first started. It is plausible they could also caust weight loss, espeically considering they cause nausea and anorexia. However, the data on weight loss from randomized controlled trials is very limited and inconclusive, so we did a very large observational study in a real-world of the VA national healthcare system who were newly started on these medications, to see if they were associated with weight loss.
We found that patient with dementia started on cholinesterase inhibitors had a substantially higher risk of clinically significant weight loss over a 12-month period compared to matched controls.
1,188 patients started on cholinesterase inhibitors were matched to 2,189 similar patients who were started on other new chronic medications. The primary outcome was time to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be clinically meaningful – not only noticed by a clinician but would perhaps prompt further action in considering the causes of the weight loss and medical work-up.
We found that starting cholinesterase inhibitors was associated with a 24% greater risk of developing weight loss. Overall, 29% of patients started on cholinesterase inhibitors experienced a weight loss of 10 pounds or more, compared with 23% of the control group. This corresponds to a number needed to harm of 21 over 1 year; meaning only 21 patients need to be treated with a cholinesterase inhibitor over the course of a year for one patient to experience a 10 pound weight loss.
MedicalResearch.com Interview with:
Dr. Li-Huei Tsai Ph.D.
Professor and Director - Picower Institute
For Learning and Memory
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology
Medical Research: What is the background for this study? What are the main findings?
Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage.
In this regard, our study reports three major findings:
(1) Physiological neuronal activity itself results in the formation of DNA breaks;
(2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory;
(3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation.
MedicalResearch.com Interview with: Kelvin TSOI BSc, PhD Research Associate Professor, Stanley Ho Big Data Decision Analytics Research Centre Associate Professor (by Courtesy), School of Public Health and Primary Care Faculty of Medicine The Chinese University of Hong Kong MedicalResearch: What is the background for this study? What are the main findings? Dr. Tsoi: Dementia is a...
MedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center
MedicalResearch: What is the background for this study?
Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.
MedicalResearch: What are the main findings?
Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.
In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.
MedicalResearch.com Interview with:
Dr. Fredrik Jernerén PhD
Postdoctoral Research Fellow
Department of Pharmacology
University of Oxford
Oxford, United Kingdom
Medical Research: What is the background for this study? What are the main findings?
Dr. Jernerén: Development of dementia and Alzheimer’s disease is associated with an accelerated rate of brain shrinkage. Identifying ways to reduce the brain atrophy rate at an early stage may offer new strategies to prevent or delay the onset of dementia. In this study on elderly subjects diagnosed with Mild cognitive impairment (MCI), who are at increased risk of developing dementia, we investigated whether the effect of B vitamin supplementation on reducing the brain atrophy rate was influenced by circulating levels of omega-3 fatty acids. We have found that this indeed was the case. The higher the baseline concentration of the combined omega-3 fatty acids (DHA+EPA), the greater the protective effect of the B vitamin treatment. In subjects with high omega-3 concentrations who at the same time had elevated homocysteine levels (indicating a lack of B vitamins), B vitamin treatment reduced the brain atrophy rate by about 70% compared with the placebo group.
Associate Professor Lim Lee Wei (Sunway University, Malaysia) and Assistant Professor Ajai Vyas (Nanyang Technological University, Singapore) discover a new treatment using deep brain stimulation of the Prefrontal Cortex for dementia.[/caption]
MedicalResearch.com Interview with: Dr. Lim Lee Wei
School of Biological Sciences, Nanyang Technological University, Singapore;
Department of Biological Sciences, Sunway University, Malaysia
Medical Research: What is the background for this study? What are the main findings?
Response: To date, pharmacological treatments for dementia have limited effects (most of the drugs failed in the second or third clinical trials) and there are no known treatments that cure or delay the progression of this memory impairment. Therefore, a novel non-pharmacological approach such as deep brain stimulation (DBS) is currently considered as an alternative treatment to reduce the symptomatic and progression of this memory deterioration.
Deep brain stimulation for dementia-related disease is currently evaluated as a potential therapy. In line with this development, evidence from recent studies suggests that deep brain stimulation might enhance memory functions when particular brain areas are stimulated. Of particular interest in our study, electrical stimulation of the Prefrontal Cortex induced striking antidepressant activity in both patients and animals studies (see our recent study, Lim et al., 2015 Translational Psychiatry; http://www.nature.com/tp/journal/v5/n3/full/tp201524a.html). However, no studies have shown the putative role of Prefrontal Cortex deep brain stimulation in learning and memory performance. In our finding, we have shown that deep brain stimulation of this region (Prefrontal Cortex) improved the short-term and long-term memory by a very important mechanism, which led to the formation of new brain cells in another region of the brain called the hippocampus, which is also involved in memory. Therefore, our findings suggest that deep brain stimulation of the Prefrontal Cortex has the potential to be developed into a therapy to treat dementia and other conditions that lead to memory loss in humans.
MedicalResearch.com Interview with:
Donovan Maust, MD, MS
Assistant Professor of Psychiatry
University of Michigan
Research Scientist, Center for Clinical Management Research
VA Ann Arbor Healthcare System
Medical Research: What is the background for this study? What are the main findings?
Dr. Maust: From a recent government report, we known that about 1/3 of older adults with dementia in nursing homes and about 14% of those in the community have been prescribed an antipsychotic. While providers focus on what benefit the treatment they offer, it is important to also be aware of the potential harms, particularly when it is death. Prior estimates came from relatively short studies and showed a 1% increase. This paper finds that, over 180 days, the increased mortality comparing antipsychotic users to matched non-users is about 2 to 5 times higher.
MedicalResearch.com Interview with:
Peter Bayley PhD
War Related Illness and Injury Study Center
Veteran Affairs Palo Alto Health Care System
Palo Alto, California
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Bayley: There is currently widespread interest and debate surrounding the topic of screening for Alzheimer’s disease and other types of dementia The study describes results from National Memory Screening Day in 2010, an annual community event sponsored by the Alzheimer Foundation of America. Face-to-face screening takes place in a private setting; only the individual being tested and the screener are present. The memory screening consists of one of seven validated cognitive tests: the GPCOG (General Practitioner Assessment of Cognition), MINI-COG, MIS (Memory Impairment Screen), the BAS (Brief Alzheimer’s Screening), Kokmen Short Test of Mental Status, Mini-Mental State Examination, Montreal Cognitive Assessment, or the Saint Louis University Mental Status Examination. Participants with scores below cutoff for possible dementia are encouraged to bring the results to their healthcare professional for follow-up and/or inclusion in medical files.
We report the results from a subset of 3,064 participants. Overall, 11.7% failed one of the memory screening tests. As expected, failure rates were higher in older and less-educated participants (P’s < .05). Subjective memory concerns were associated with a 40% greater failure rate for persons of similar age and education but no memory concerns (odds ratio = 1.4, 95% confidence interval = 1.07–1.78). However, most individuals who expressed concern about their memories passed the screening tests (54-96%, depending on age and education).
MedicalResearch.com Interview with:
Shelly L. Gray, PharmD, MS
Professor of Pharmacy
School of Pharmacy, University of Washington, Seattle
Medical Research: What is the background for this study? What are the main findings?
Dr. Gray: Many medications have anticholinergic effects such as those used to treat overactive bladder, seasonal allergies, and depression. The general view is that anticholinergic-induced cognitive impairment is reversible, however, emerging evidence suggests that these medications may be associated with increased dementia risk. We conducted a prospective population-based cohort study in 3434 older adults to examine whether cumulative anticholinergic medication use is associated with increased risk of incident dementia. Using automated pharmacy data, we found that higher 10-year cumulative dose was associated with increased risk for dementia and Alzheimer disease over an average of 7.3 years of follow-up. In particular, people with the highest use (e.g. taking the equivalent of oxybutynin 5 mg/day or chlorpheniramine 4 mg/day for longer than 3 years) were at greatest risk.
MedicalResearch.com Interview with:
Raquel C. Gardner, MD, Research Fellow
San Francisco VA Medical Center
Clinical Instructor
Memory and Aging Center, Department of Neurology
University of California, San Francisco
Medical Research: What are the main findings of the study?
Dr. Gardner: We found that people who experience a traumatic brain injury (TBI )when they are 55 or older have a 26% higher chance of getting dementia over the next 5 to 7 years compared to people who experience bodily trauma.
MedicalResearch.com Interview with:
Richard J. Kryscio, PhD, Professor
Sanders-Brown Center on Aging
University of Kentucky
Medical Research: What are the main findings of the study?
Dr. Kryscio: We followed 531 elderly over time assessing their cognition annually; of these 105 (about 20%) eventually were diagnosed with a serious cognitive impairment (either a mild cognitive impairment or a dementia) and 77% of the latter declared a subjective memory complaint prior to the diagnosis of the impairment. In brief, declaration of a memory problem put a subject at three times the risk of a future impairment.
MedicalResearch.com Interview with:
Dr. Claire Sexton Ph.D.
University of Oxford
Medical Research: What are the main findings of the study?
Dr. Sexton: We found that sleep difficulties (which can include trouble falling asleep, waking up during the night, or waking up too early) were associated with an increased rate of decline in brain volumes over 3-5 years.
Medical Research Interview with:
Neha P. Gothe, PhD
Division of Kinesiology, Health and Sport Studies
Wayne State University
Detroit, MI 48202.
Medical Research: What are the main findings of the study?
Dr. Gothe: The yoga group was speedier and more accurate on tests of information recall, mental flexibility and task-switching than it had been before the intervention. Participants in the yoga group showed significant improvements in working memory capacity, which involves continually updating and manipulating information. They were also able to perform the task at hand quickly and accurately, without getting distracted.
MedicalResearch.com Interview with:
Dr. Caroline E Stephens PhD
Department of Community Health Systems
University of California, San Francisco
Medical Research: What are the main findings of the study?
Dr. Stephens: In our national random sample of nursing home residents, we found that mild cognitive impairment (CI) predicted higher rates of ED visits compared to no CI, but interestingly, ED visit rates decreased as severity of cognitive impairment increased. However, after nursing home residents were evaluated in the ED, severity of CI was not significantly associated with higher odds of hospitalization.
Another important finding was that the proportion of nursing home residents using feeding tubes more than tripled in advanced or end-stage dementia, from 9.9% to 33.8%. Moreover, tube-fed nursing home residents had 73% higher rates of total ED visits, but once evaluated in the ED, they were no more likely to be hospitalized than those without feeding tubes. This finding is particularly striking given the numerous existing studies that have questioned the utility and appropriateness of using feeding tubes in people with advanced dementia.
MedicalResearch.com Interview with:
James T. Becker, Ph.D.
Professor of Psychiatry, Psychology, and Neurology
University of Pittsburgh
Medical Research: What are the main findings of the study?
Dr. Becker: We found that people who eat baked or broiled (but not fried) fish at least once every week had significantly larger brain volumes in areas critical for memory and cognition, namely, hippocampus, precuneus, posterior cingulate cortex, and orbital frontal cortex.
MedicalResearch.com Interview with:
Kumar Bharat Rajan, PhD
Assistant Professor
Department of Internal Medicine
Section of Population Sciences
Chicago IL 60612
Medical Research: What are the main findings of the paper?
Dr. Rajan: Lower levels of cognitive functioning was associated with incident stroke and the change in cognitive functioning was increased after incident stroke. Cognitive functioning was an independent marker of mortality even after accounting for incident stroke.
MedicalResearch.com Interview Invitation
Dr. Bryan K. Woodruff
Assistant Professor of Neurology
Mayo Clinic, Arizona
Medical Research: What are the main findings of the study?
Dr. Woodruff: There is evidence in the medical literature supporting a negative impact of losing a spouse for health conditions such as cancer or cardiovascular disease, but this has not been evaluated in terms of the impact of widowhood on the development of dementia. We used the National Alzheimer’s Disease Coordinating Center (NACC) database, which pools data gathered by multiple federally-funded Alzheimer’s disease research centers to try to answer this question. Specifically, we looked at the age at which individuals ultimately developed dementia in both individuals who lost their spouse and in those who remained married over the course of the study. Surprisingly, the data we analyzed did not support a negative impact of losing a spouse in individuals who had no cognitive difficulties when they entered the study, and we saw a paradoxical effect of widowhood in those with mild cognitive impairment (MCI).
MedicalResearch.com Interview with:
Prashanthi Vemur, Ph.D.
Mayo Clinic
Rochester, Minnesota
MedicalResearch: What are the main findings of the study?
Dr. Vemuri: Lifetime intellectual enrichment might delay the onset of cognitive impairment and be used as a successful preventive intervention to reduce the impending dementia epidemic. We studied two non-overlapping components of lifetime intellectual enrichment: education/occupation-score and mid/late-life cognitive activity measure based on self-report questionnaires. Both were helpful in delaying the onset of cognitive impairment but the contribution of higher education/occupation was larger.
MedicalResearch.com Interview with:
Regina Shih PhD
Senior Behavioral Scientist at the RAND Corporation.
MedicalResearch: What are the main findings of the study?
Dr. Shih: RAND identified 25 high-impact policy options to improve the delivery, workforce, and financing of long term care, with a specific eye toward those with dementia and their caregivers. Undertaking these 25 policy options would achieve five goals: increasing public awareness of dementia and its signs and symptoms; improving access to long-term care; promoting high-quality, person-centered care like that offered at Lakeside Manor; providing better support for family caregivers; and reducing the burden of dementia costs on individuals and their families.
Of these 25 policy options, we identified four unique options that have never been identified in any national plan on dementia or long-term care. This is likely because we focused on the intersection between dementia and long-term care, rather than just one or the other. And, rather than only focusing on actions that federal agencies can take, we identified policy options by interviewing 30 different stakeholders in the public and private sectors at the local, state, and national levels. These unique, high-impact policy options have to do with
MedicalResearch.com Interview with:
Dr. Anna-Maija Tolppanen PhD
Department of Neurology
University of Eastern Finland, Kuopio
MedicalResearch: What are the main findings of the study?
Dr. Tolppanen: Persons who had higher levels of cynical distrust were about three times more likely to develop dementia over eight-year follow-up.
MedicalResearch.com Interview with
T. Jared Bunch, MD
Medical director for Heart Rhythm Services
Director of Heart Rhythm research
Intermountain Medical Center, Utah
MedicalResearch: What are the main findings of the study?
Dr. Bunch: The main findings of the study are:
1) Atrial fibrillation patients treated with warfarin anticoagulation that have lower percentages of time in therapeutic range have significantly higher risks of all forms of dementia.
2) The dementia relative risk related to lower percentages of time in therapeutic range was higher than all other variables associated with stroke or risk of bleeding.
3) The risk of dementia related to lower percentages of time in therapeutic range was highest in younger patients in the study (<80 years).
MedicalResearch.com Interview with:
Tara Lagu MD PhD
Assistant Professor of Medicine
Tufts University School of Medicine
MedicalResearch.com: What are the main findings of the study?
Dr. Lagu: We found that use of mechanical ventilation in patients 65 and older is increasing rapidly. If current rates of increase continue, we expect that by 2020 there will be more than 600,000 hospitalizations per year that involve mechanical ventilation. This is a doubling in 20 years (2001-2020), and represents demand that could easily exceed the capacity of the US critical care system. We also found that increase in use among patients with dementia is 4 times faster than those without dementia. This is important because dementia is a terminal illness, and use of mechanical ventilation in patients with end-stage dementia is associated with poor 30-day and 1-year outcomes.