Neuropathologic changes at age 90+ related to sleep duration 19 to 40 years earlier: The 90+ Study.

INTRODUCTION: We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study. METHODS: Participants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: In 264 participants, mean age at sleep self-report was 69 years, mean age at autopsy was 98 years, and mean interval between sleep self-report and autopsy was 29 years (range: 19-40). Those reporting > 8 hours of sleep had lower likelihood of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) inclusions (OR = 0.18; CI = 0.04-0.82) and amyloid beta deposits (OR = 0.34; 95% CI = 0.12-0.94). DISCUSSION: Long self-reported sleep is associated with lower odds of neurodegenerative neuropathologic changes 19 to 40 years later in the oldest-old, suggesting a potential role of sleep in accumulation of dementia-related neuropathologies. HIGHLIGHTS: Association of self-reported sleep with non-Alzheimer's disease neuropathologic changes has not been explored. Whether sleep duration is related to dementia neuropathologic changes decades later is unclear. Long self-reported sleep is associated with lower odds of Alzheimer's disease neuropathologic change 19 to 40 years later in the oldest-old. Long self-reported sleep is associated with lower odds of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change 19 to 40 years later in the oldest-old.

Characterizing Limbic-Predominant Age-Related TDP-43 Encephalopathy Without Alzheimer's Disease and Lewy Body Dementia in the Oldest Old: A Case Series.

BACKGROUND: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a clinicopathological construct proposed to facilitate studying TDP-43 pathology in older individuals. OBJECTIVE: Our aim was to describe clinical and cognitive characteristics of LATE-NC without Alzheimer's disease neuropathologic change (ADNC) and Lewy body (LB) and to compare this with ADNC and primary age related tauopathy (PART). METHODS: In 364 autopsies of the oldest old of The 90+ Study, we identified those with LATE-NC without ADNC and LB. Control groups were participants with ADNC and PART. RESULTS: Of 31% of participants who had LATE-NC, only 5 (1.4%) had LATE-NC without ADNC and LB, all of whom had tau. These participants had a gradual and progressive cognitive decline. Four (80%) had dementia at death, a rate that was higher than ADNC (50%) and PART (21.7%). Mean duration of cognitive impairment was twice as long in LATE-NC without ADNC and LB (6.2 years) compared to ADNC (2.9 years) and PART (3 years). LATE-NC without ADNC and LB group had a higher prevalence of syncope, depression, and extrapyramidal signs than the ADNC and PART groups. CONCLUSIONS: Despite the high prevalence of LATE-NC, LATE-NC without ADNC and LB was rare in this large oldest-old cohort, highlighting the very high prevalence of multiple pathologic changes in the oldest old. Slowly progressive cognitive decline, ubiquitous memory impairment, history of syncope and depression, and extrapyramidal signs were prominent features among our LATE-NC without ADNC and LB group.

Self-reported sleep in relation to risk of dementia a quarter of a century later at age 90+: The 90+ Study.

OBJECTIVE: To examine sex-specific associations of sleep duration and napping self-reported at mean age of 69 years (range: 53-81) with risk of incident dementia 24 years later at age 90 +. METHOD: Analytic sample included individuals from a population-based study who reported sleep and napping once in the 1980s and 24 years later (range: 16-38) joined The 90+ Study and were evaluated in-person. Those without dementia at baseline of The 90+ Study were prospectively followed. Hazard ratios [HR] and 95% confidence intervals [CI] of dementia risk were estimated by Cox regression. RESULTS: Of 574 participants 71% were women, mean age at start of dementia follow-up with The 90+ Study was 93 years (range: 90-102). After 3.3 years (range: 0.4-13.8) of follow-up 47% developed dementia. Higher risk of dementia at age 90+ was seen in women with <6 hours of self-reported sleep per night (adjusted HR = 2.00; 95% CI = 1.15-3.50; p = .01) compared with 8 hours. Lower risk of dementia at 90+ was seen in men with short-to-moderate (<60 minutes) self-reported naps compared with no naps (HR = 0.33; 95% CI = 0.18-0.63; p < .01). CONCLUSIONS: Sleep and nap 24 years earlier are important risk factors for dementia after age 90.

Cognitive resilience to three dementia-related neuropathologies in an oldest-old man: A case report from The 90+ Study.

Cognitive resilience provides insights into maintaining good cognition despite dementia-related neuropathologic changes. It is of special interest in the oldest-old (age 90+) because age is the strongest risk factor for dementia. We describe the only participant of The 90+ Study, among 367 autopsies, who maintained normal cognition despite intermediate-high levels of 3 dementia-related neuropathologic changes, advanced age, and comorbidities associated with cognitive impairment. This man remained cognitively normal throughout 13 semi-annual study visits, last one being 4 months before his death at 96. His cognitive test scores remained around the 90th percentile for non-timed tests and declined from 90th to 50th percentile (significant for semantic fluency) for timed tests. He remained physically and cognitively active until death, despite extrapyramidal signs in the last year of life. Neuropathological examination revealed intermediate level of Alzheimer's disease neuropathologic change (Thal phase 5, Braak NFT stage IV, CERAD score 3), Lewy bodies and neurites in the olfactory bulb, brainstem and limbic areas (Braak PD stage 4), TDP-43 inclusions in the amygdala and hippocampus (LATE stage 2), and a microvascular lesion in putamen. This case demonstrates that cognitive impairment is not inevitable even in the oldest-old with mutltiple dementia-related neuropathologic changes.

Norms and equivalences for MoCA-30, MoCA-22, and MMSE in the oldest-old.

BACKGROUND: Cognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group. AIMS: To provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old. METHODS: Data on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants. RESULTS: MoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16. DISCUSSION AND CONCLUSIONS: Subtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests.

Cross-Cultural Comparison of Rural Healthy Adults: Russian and American Groups.

OBJECTIVE: The Russian-speaking population is among the largest European-born in the U.S., yet Russian-American cross-cultural research is scarce. Two studies compared neuropsychological test performance in Russian and American urban adults. However, rural populations of the two nations have never been compared. Cross-cultural neuropsychological differences in rural populations might present differently than in urban dwellers. The present study provides a cross-sectional comparison of neuropsychological test performance in Russian and American rural adults. METHODS: Neuropsychological test performance of 51 American (67% female) and 52 Russian (60% female) healthy rural adults age 18-89 was compared using t-test with Bonferroni correction for education-adjusted z-scores for the following tests: Rey Complex Figure Test (RCFT), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test A and B (TMT A&B), Stroop Neuropsychological Screening Test, Benton Judgment of Line Orientation Test (JLO), Brief Visuospatial Memory Test-Revised (BVMT-R), Color Trails Test 1 and 2 (CTT 1&2), WMS-IV Logical Memory Test (LMT), WAIS-IV Digit Span Forward (DSF) and Backward Test (DSB), and Symbol Digit Modalities Test (SDMT). RESULTS: Age and sex distribution did not differ in the two groups, but the Russian group was more highly educated. The American group outperformed the Russian group on TMT B, CTT 2, recognition trials of RCFT, BVMT-R, LMT, and on DSF. CONCLUSIONS: Cultural differences in attitudes to timed activities, experience with timed tests and multiple-choice format, attention to details, and length of digit-words that put differential demand on short-term memory in Russian and in English may mediate observed between-group differences.

Neuropsychological Test Norms in Cognitively Intact Oldest-Old.

OBJECTIVES: Individuals aged 90 or older (oldest-old), the fastest growing segment of the population, are at increased risk of developing cognitive impairment compared with younger old. Neuropsychological evaluation of the oldest-old is important yet challenging in part because of the scarcity of test norms for this group. We provide neuropsychological test norms for cognitively intact oldest-old. METHODS: Test norms were derived from 403 cognitively intact participants of The 90+ Study, an ongoing study of aging and dementia in the oldest-old. Cognitive status of intact oldest-old was determined at baseline using cross-sectional approach. Individuals with cognitive impairment no dementia or dementia (according to DSM-IV criteria) were excluded. Participants ranged in age from 90 to 102 years (mean=94). The neuropsychological battery included 11 tests (Mini-Mental Status Examination, Modified Mini-Mental State Examination, Boston Naming Test - Short Form, Letter Fluency Test, Animal Fluency Test, California Verbal Learning Test-II Short Form, Trail Making Tests A/B/C, Digit Span Forward and Backwards Test, Clock Drawing Test, CERAD Construction Subtests), and the Geriatric Depression Scale. RESULTS: Data show significantly lower scores with increasing age on most tests. Education level, sex, and symptoms of depression were associated with performance on several tests after accounting for age. CONCLUSIONS: Provided test norms will help to distinguish cognitively intact oldest-old from those with cognitive impairment. (JINS, 2019, 25, 530-545).

Exploring predictors of life satisfaction and happiness among Siberian older adults living in Tomsk Region.

Despite the growing interest in studying factors affecting subjective well-being of older adults, little research has been conducted on vast territory of Siberia (Russia) with large population. To address this lack of evidence, we explored the relationship between subjective well-being and social aspects (social and emotional support, social network, and social activities), living conditions (standards of living and residence area), self-reported health, and demographic characteristics in older adults living in Tomsk Region, Siberia. Subjective well-being was measured by life satisfaction and happiness (each measured with one 11-point question). Sample included 489 community-dwelling respondents, aged 65 or older. We found that mean life satisfaction and happiness reported by our respondents were lower than those of European countries. Higher quality of social interaction, better standards of living, and being satisfied with own health were associated with higher life satisfaction and happiness. This study provides original data on a region barely investigated and suggests that Siberian older adults receive strong benefits from social support and from social network and that similar factors are related to subjective well-being both in Siberian and Eastern European older adults. Future studies should further explore the relationship between different kinds of social support (e.g., psychological vs. material support) and subjective well-being in different Siberian ethnic groups or regions.

A comparison of neuropsychological performance between US and Russia: preparing for a global clinical trial.

BACKGROUND: Understanding regional differences in cognitive performance is important for interpretation of data from large multinational clinical trials. METHODS: Data from Durham and Cabarrus Counties in North Carolina, USA and Tomsk, Russia (n = 2972) were evaluated. The Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (Trails B), Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (WLM) delayed recall, and self-report Alzheimer's Disease Cooperative Studies Mail-In Cognitive Function Screening Instrument (MCFSI) were administered at each site. Multilevel modeling measured the variance explained by site and predictors of cognitive performance. RESULTS: Site differences accounted for 11% of the variation in the MoCA, 1.6% in Trails B, 1.7% in WLM, and 0.8% in MCFSI scores. Prior memory testing was significantly associated with WLM. Diabetes and stroke were significantly associated with Trails B and MCFSI. CONCLUSIONS: Sources of variation include cultural differences, health conditions, and exposure to test stimuli. Findings highlight the importance of local norms to interpret test performance.