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Alzheimer’s Association International Conference

Access timely, concise peer-reviewed reports from the Alzheimer’s Association International Conference selected by the Neurology Today editors.

Monday, July 22, 2019

LOS ANGELES—Impairment of multiple senses is associated with a significantly increased risk of dementia, according to findings presented here at the Alzheimer's Association International Conference.

Researchers said the findings suggest that even mild sensory impairments, when considered together, were associated with cognitive decline, highlighting the importance for more research on the topic.

The investigators examined data from the National Institutes of Health's Health, Aging and Body Composition (Health ABC) study, which includes white and African-American people, ages 70 to 79 at enrollment. A total of 1,818 participants, who had sensory assessments at baseline, were followed for about 11 years, said Willa Brenowitz, PhD, MPH, a post-doctoral fellow at the University of California, San Francisco.

In Health ABC, the researchers assessed vision, smell, hearing, and touch with a battery of tests. Patients in the best performing quartile of each domain were scored as 0 for that domain, the next quartile of impairment were scored as 1, and so on. Then the scores were added up, ranging from 0 to 12, with 12 as the most impaired.

The researchers used the Modified Mini-Mental State Examination and Digit Symbol Substitution test to assess dementia. Incident dementia was based on hospitalization records, dementia medications, and at least a 1.5-point standard deviation decline on the Modified Mini-Mental State Examination.

About 80 percent of those who had the least sensory impairment—those who had scores of 0 to 4 out of 12—were dementia-free at 10 years, researchers found. Each quartile of worse impairment had a lower percentage of dementia-free study participants than the quartile before. In the group with the most sensory impairment—those with scores of 9 to 12—only 60 percent were dementia-free at 10 years, investigators found.

Each 4-point difference in sensory score meant an annual rate of decline of 0.3 points on the 0- to 100-point Modified Mini-Mental State Examination and on the 0- to 91-point DSS, Dr. Brenowitz said.

"Each sensory impairment might have a different etiology that explains its association with dementia, but I think there's this evidence that combining them has a strong association, which hasn't been researched much," Dr. Brenowitz said. "So I think it's an interesting area. The biggest question that remains is whether sensory impairments are potentially modifiable and could impact risk of dementia or whether it's just a pre-clinical indicator of dementia."

She said she and her colleagues, including senior author Kristine Yaffe, MD, are continuing to examine the data. Among other things, they'll be looking at whether there are particular combinations of impairments that are especially important for increased risk of dementia.

David A. Bennett, MD, director of the Rush Alzheimer's Disease Center, said there is a lot of research interest in sensory impairment and dementia; however, much of it is focused on smell, hearing, and vision, but not on touch, which this study incorporates.

"This is a new twist to add them up but the results are not surprising," he said.

"What we don't know from the abstract but would hope to see addressed in the paper is whether these are four relatively unrelated factors that simply have additive effects or whether they are correlated and represent a group of interrelated factors suggesting some common underlying biology."

The findings might be useful broadly but not necessarily for individual care, he said.

"This is a large longitudinal study that has relevance for public health and research," Dr. Bennett said. "The effects are too small to be actionable at the individual level."

Drs. Brenowitz and Bennett reported no disclosures.

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Regan J, Frison E, Collin F, et al. Individualised sensory intervention to improve quality of life in people with dementia and their companions (SENSE-Cog trial): Study protocol for a randomised controlled trial. Trials 2019; 20(1):80.

Monday, July 22, 2019

LOS ANGELES—Healthy lifestyle habits have a compounding effect in reducing the risk of Alzheimer's dementia, according to a combined analysis of two large data sets presented here at the Alzheimer's Association International Conference.

Researchers at Rush University examined data from the Chicago Health and Aging Project and the Rush Memory and Aging Project comprising approximately 2,800 participants ranging from 58 to 98 years old; they were followed up for more than an average of 5.8 and six years, respectively.

The research team created healthy, or low-risk, lifestyle scores for participants based on whether they were non-smokers; participated in at least 150 minutes per week of moderate to vigorous leisure physical activity such as walking for exercise, bike riding or swimming; consumed light to moderate amounts of alcohol; reasonably adhered to the MIND diet of vegetables, nuts, seafood and other healthy foods and avoided certain, unhealthy foods; and engaged in late-life cognitive activities such as reading books, playing checkers, or even watching TV.

They created hazard ratios for Alzheimer's dementia risk after adjusting for age, sex, race, education, apolipoprotein e4 status, and history of cardiovascular disease.

Each healthy lifestyle factor reduced the risk of dementia by 27 percent, said Klodian Dhana, MD, PhD, assistant professor of internal medicine at Rush University.

They also found that, compared with participants following none or one of the lifestyle factors, the risk of incident Alzheimer's dementia was 37 percent lower for those following two or three of the factors (HR: .63; 95% CI: .47 - .84), and 60 percent lower for those following four or five lifestyle choices (HR: .40; 95% CI: .28 -.56).

"These associations were largely similar across gender and race," researchers said. But they were slightly modified by apolipoprotein e4 status in the Chicago Health and Aging cohort, they said.

"I think neurologists may encourage their patients to consume more vegetables, particularly leafy greens, and to replace red meat with poultry and avoid fried foods," Dr. Dhana said. "Up to one glass of wine in a day could be beneficial for older adults who do not have contraindications and in combination with a healthy diet and not smoking cigarettes."

He added that maintaining optimized physical and mental health is "a necessity for the elderly, and therefore, neurologists should recommend that patients participate in aerobic exercises, walk to libraries, read books, and play games like cards and crosswords."

David S. Knopman, MD, FAAN, professor of neurology at Mayo Clinic in Rochester, MN, said the results are "informative and likely valid."

"These various risk factors are indeed important for lowering dementia risk and they do so through a variety of mechanisms, but there is no evidence that any of them reduce amyloid-beta accumulation or tau accumulation, the two key Alzheimer's-defining processes.

"There is much evidence from the cardiovascular world—the 'Simple 7' of the American Heart Association—that also shows that adherence to as many healthy behaviors as possible has an additive benefit," he said. "I don't think that these data in the hands of neurologists seeing already-symptomatic people are all that helpful. Instead, this kind of information needs to be disseminated to the middle-aged lay public as well as primary care physicians."

He said the results should be described as lowering the risk of "dementia" rather than "Alzheimer's dementia." The term "Alzheimer's dementia" used by the researchers could be confusing, he said.

"Their use of the term 'Alzheimer's dementia' would imply to most readers that adherence to these various behaviors affects the burden of beta-amyloid neuritic plaques and tau-containing neurofibrillary tangles," he said. "In fact, the clinical diagnoses in these individuals is actually dementia and the authors generally have no direct evidence that all of the cases had plaques and tangles."

"Probably most do," he added, but he said that a considerable proportion of cases characterized as Alzheimer's dementia have been shown in prior research, including by Rush researchers, to have cerebrovascular or other non-AD pathologies.

Drs. Dhana and Knopman reported no disclosures.

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Lourida I, Hannon E, Littlejohns TJ, et al. Association of lifestyle and genetic risk with incidence of dementia. JAMA 2019; Epub 2019 July 14.

Monday, July 22, 2019

LOS ANGELES—The first federally funded clinical study is underway to specifically assess interventions for lesbian, gay, bisexual, queer, and transsexual (LGBQT) people with dementia involves culturally sensitive coaching on exercise, communication, problem-solving, and other skills, according to a review of the project here at the Alzheimer's Association International Conference.

The study will test how specially tailored coaching sessions improve outcomes such as physical activity and quality of life for LGBQT patients with dementia, compared with LGBQT patients who receive standard coaching without the specialized approach, said Hyun-Jun Kim, PhD, a research scientist at the University of Washington in Seattle and a co-investigator on the project, known as the Aging with Pride IDEA (Innovations in Dementia Empowerment and Action).

"It is essential to ensure programs are responsive to the needs of LGBQT older adults with dementia," said Dr. Kim, who is working with principal investigator Karen Fredriksen Goldsen, PhD.

The trial is a breakthrough in the field of LGBQT health care, Dr. Kim said. Over the last decade, national health surveys have started gathering information on sexual orientation and gender identification, enabling researchers to examine data on their health status and health care challenges. Among their observations, they have found that the LGBQT population has an elevated risk for poor health and disability, in general, and older adults in the LGBQT community are at a higher risk of HIV/AIDS, smoking, and depression—all risk factors for dementia.

In 2017, findings from the Aging with Pride National Health, Aging, and Sexuality/Gender Study showed that 85 percent of the LGBQT participants reported discrimination or victimization at least once in their lives, and 69 percent at least three times. Twenty-two percent of participants also reported inferior health care or denial of health care; 58 percent reporting living alone; 65 percent reported having no partner or spouse; and 85 percent reported close friends as their support network.

The researchers also found that physical activity was significantly associated with physical functioning and health-related quality of life and that socializing with friends and family was significantly tied to that quality of life.

These findings formed the basis for the IDEA project discussed at the conference and scheduled for completion in 2021.

Researchers hope to include 150 pairs of coaches and patients, along with their caregivers. They will be randomized to receive standard coaching or "enhanced" coaching on exercise, including balance, strengthening, and endurance; dementia education; realistic expectations; communication skills; problem-solving skills; and increasing pleasant events. There will be two 60-minute coaching sessions per week for three weeks, then one 60-minute session a week for three more weeks, and then a 15-minute follow-up session by phone once a month for four months.

The "cultural empowerment" aspect of the coaching is meant to help participants stay engaged with the program, Dr. Kim said. This empowerment, he said, is "necessary to address the LGBQT-specific needs, including difficulties in building trust due to stigma and identity concealment."

Holly E. Hinson, MD, MCR, FAAN, associate professor of neurology at Oregon Health and Science University, said the project is a welcome development for LGBQT health care.

"I think there's a growing awareness that this particular group… is worthy of specific studies," she said, referring to the establishment of sexual and gender minorities as a health care disparity group in 2016. "Tailoring intervention specifically to this patient population, as you might for other disparity groups, makes a lot of sense and would actually be very worthwhile. I'm excited that this… awareness that sexual and gender minorities have specific needs is growing."

She said that the project is an example of the new designation freeing up researchers and physicians to be able to start addressing health problems they have known were there.

"Recognizing that these social determinants of health have a huge impact for patients is a huge step forward for us as not only as a research community but also as a community providing high-quality health care, because that's exactly what we want to combat—to reduce some of these disparities that we know exist."

Drs. Kim and Hinson reported no disclosures.

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Goldsen KF, Kim HJ, Jung H, Goldsen J. The Evolution of Aging with Pride—National Health, Aging, and Sexuality/Gender Study: Illuminating the iridescent life course of LGBTQ adults aged 80 years and older in the United States. Int J Aging Human Dev 2019; 88(4):380–404.

Monday, July 22, 2019

LOS ANGELES—Sexual and gender minorities (SGM) are 29 percent more likely than those who are not in those groups to report that they have experienced subjective cognitive decline in the past year, according to results from a cross-sectional telephone survey presented here at the Alzheimer's Association International Conference.

SGM is an umbrella term comprising individuals who are lesbian, gay, bisexual, and transgender as well as those whose sexual orientation or reproductive development varies from traditions and norms.

Researchers at the University of California, San Francisco—who conducted the study using data from nine states included in the Behavioral Risk Factor Surveillance System—said the findings on point to the need for further exploration of the early signs of cognitive decline among sex and gender minorities.

Subjective cognitive decline—the self-perception that one has experienced more frequent or worsening confusion or memory loss in the past year—puts people at three times greater risk for later cognitive decline; 2 to 7 percent of those who report this perception progress to Alzheimer's disease annually.

"The hope is that this raises awareness of the need for screening for the community," said Jason Flatt, PhD, MPH, assistant professor of public health at the University of California, San Francisco. "Nationally we're seeing a huge demographic shift, with the population getting older and older. So likely we need to really think about this community in terms of Alzheimer's and other dementia prevention. There are a lot of things we could be doing."

Dr. Flatt pointed to an array of challenges facing members of this community that make it especially imperiled when dementia symptoms arise. They are less likely to be married or have children, they are twice as likely to live alone, and they have little to no caregiver support, he said. The community also struggles with stigma, discrimination, and trauma and tends to be reluctant to seek medical care.

The study analyzed data on 44,400 adults—about 1,300 in the sexual and gender minority community—ages 45 and older in Nevada, Minnesota, Wisconsin, Illinois, Ohio, West Virginia, Virginia, Georgia, and Hawaii. Those in the SGM group were significantly less likely to be married, more likely to be a racial or ethnic minority, had significantly fewer years of education, were significantly more likely to be unemployed, and significantly more likely to be in a low-income group and to be uninsured.

One in seven SGM adults reported subjective cognitive decline, compared to one in 10 non-SGM participants. After accounting for personal background characteristics such as age and income, researchers found, SGM adults were 29 percent more likely to report subjective cognitive decline. They were also more likely to report giving up day to day activities (p=.003) and more likely to report needing help with household tasks (p=.01).

The researchers found no difference in the percentage of SGM and non-SGM participants who reported symptoms to the doctor. More than half in both groups had not done so.

Dr. Flatt acknowledged that the questions asked in the survey amount to a screen, and are not diagnostic, and that the confusion and memory loss reported could be due to other health issues that are not dementia-related, such as depression or trouble sleeping.

 He and his group are continuing to analyze data, which will eventually encompass 24 states.

 "This requires further study really to think about the key pieces. Do they need more social support? Do they need greater prevention, or an opportunity to get screening for cognition?"

Holly E. Hinson, MD, MCR, FAAN, associate professor of neurology at Oregon Health & Science University, said it's encouraging to see research in this area expanding since sexual and gender minorities were designated as a health care disparity population by the National Institutes of Health a few years ago.

"I'm thrilled to see people are following that up and really paying attention," she said.

This study, she said, had "a very large sample size and it represented a nice cross-section of geography across the US, which is a huge benefit to the work that they did and I think distinguishes it from previous work in this area."

The subjective nature of the data calls for caution in interpreting it, however, she said.

"I'd be very interested to see in the future how this result would stack up against something a little bit more objective," Dr. Hinson said. "But it's really thought-provoking."

 Drs. Flatt and Hinson reported no disclosures.

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Flatt JD, Johnson JK, Karpiak SE, et al. Correlates of subjective cognitive decline in lesbian, gay, bisexual, and transgender older adults. J Alzheimers Dis 2018;64(1):91–102.

Monday, July 22, 2019

LOS ANGELES—A combination of personalized approaches to better calibrate the circadian clock led to some sleep quality improvements in patients with mild cognitive impairment (MCI), according to findings presented here at the Alzheimer's Association International Conference.

Researchers said the findings boost hopes that such measures could be effective in helping older people with MCI.

"By potentially intervening in this population by trying to promote their sleep quality, we may be able to promote their cognitive health as well," said Ryan Falck, MSc, a PhD candidate in the physical therapy department at the University of British Columbia, who worked on the study with Teresa Liu-Ambrose, PT, PhD.

Researchers randomized 96 patients to receive the "chronotherapy" interventions or to receive usual care and optional classes on general health. The interventions included bright light therapy that involved a kind of blue light as an external time cue to help shift 

someone's biological clock forward or backward, depending on their individual profile seen at baseline. Researchers also counseled the intervention group to boost physical activity, with goals based on baseline activity measured with a wearable device. They also provided education on good sleep hygiene, such as not watching TV too late and avoiding light at certain times of day.

The group receiving the interventions outperformed the control group, particularly at 12 weeks. At that time point, those in the intervention group maintained their sleep efficiency (p=.01); maintained the amount of sleep disruption they were experiencing at baseline (p<.01); and maintained the amount of time they stayed awake after beginning to attempt sleep. The control group worsened in those domains over the 12 weeks.

There were no significant differences in those measures at 24 weeks. Falck said the adherence to the bright light therapy fell off after 12 weeks. Patients might have felt it was onerous, he said, because it required one hour of the lighting in the morning and one hour in the evening, and that might account for the drop-off in effect at 24 weeks.

The intervention group had better scores on the Pittsburgh Sleep Quality Index, which involves a survey to gauge how well someone sleeps, than controls at 12 weeks (p<.01) and 24 weeks (p=.04). This index points to a more robust difference for the intervention group in its subjective experience of sleep quality, Falck said.

"This multimodal intervention may be beneficial for promoting both objective and subjective aspects of sleep quality," he said. Most of the research showing an association between sleep quality and cognitive function has been based on self-reporting, so subjective sleep experiences likely matter in cognitive health, he said.

"What we seem to see across the board is that people that have poorer subjective sleep are at increased risk for mild cognitive impairment and dementia," Falck said.

Kristine Yaffe, MD, professor of psychiatry, neurology and epidemiology at the University of California San Francisco, said the researchers used an approach that seems worth exploring more.

"The intervention sounds very interesting and similar strategies have been employed for other outcomes, and it seemed to help both objective and subjective sleep," she said.

She said she would like to see how well these interventions help cognition.

"I view this as a very promising and novel pilot trial for MCI," Dr. Yaffe said, "and would anticipate a larger randomized controlled trial, ideally targeting those with sleep concerns and focusing on cognitive outcomes."

Falck and Dr. Yaffe had no disclosures.

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Falck RS, Davis JC, Best JR, et al. Buying time: A proof-of-concept randomized controlled trial to improve sleep quality and cognitive function among older adults with mild cognitive impairment. Trials 2018;19(1):445.