Napping characteristics and cognitive performance in older adults.

OBJECTIVES: To determine the association of napping intention, frequency, and duration with cognition in a nationally-representative sample of US older adults. METHODS: We performed a cross-sectional analysis of community-dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013-2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past-month napping intention (intentional/unintentional), napping frequency (rarely/never [non-nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31-60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self-rated memory (score: 1[excellent]-5[very poor]). RESULTS: After adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non-nappers (B = -0.23, P < 0.01) and intentional nappers (B = -0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self-rated memory than non-nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = -0.26, P < 0.05) and CDT scores (B = -0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate-duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance. CONCLUSIONS: Among older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

The Cross-sectional and Longitudinal Associations Between IL-6, IL-10, and TNFα and Cognitive Outcomes in the Mayo Clinic Study of Aging.

BACKGROUND: Chronic inflammation has been linked with geriatric-related conditions, including dementia. Inflammatory cytokine levels, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) α, in the blood have been associated with cognitive impairment and decline. However, evidence has been mixed. METHODS: We examined the cross-sectional and longitudinal associations between baseline-measured IL-6, IL-10, and TNFα levels and the ratio of IL-6/IL-10 with cognitive test performance and mild cognitive impairment (MCI) among 1,602 community-dwelling older adults (median age = 72.8) enrolled in the Mayo Clinic Study of Aging. Approximately half (46.5%) of participants were female and 98.6% were white. At baseline and follow-up visits (occurring at 15-month intervals), participants completed neuropsychological testing, blood draws, and had a clinical consensus diagnosis. RESULTS: In multivariable cross-sectional analyses, we did not observe an association between inflammatory cytokine levels and global or domain-specific cognitive z scores; however, higher IL-6 and IL-10 levels were associated with greater odds of a MCI diagnosis. Longitudinally, we did not observe any association between inflammatory cytokine levels and cognitive test performance or risk of MCI. Sex, age, cognitive status, APOE ε4 genotype, diabetes, depression, and cerebral amyloid-beta deposition were not effect modifiers. CONCLUSIONS: These results suggest that plasma inflammatory markers may not be useful to ascertain risk for cognitive decline and MCI in the general population.

Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging.

OBJECTIVE: To determine the cross-sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics. METHODS: We examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross-sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI. RESULTS: In linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7-year follow-up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis. CONCLUSIONS: These findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

The association between peripheral total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 and functional and cognitive outcomes in the Mayo Clinic Study of Aging.

Levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, and their ratio in the blood may be useful for monitoring those at risk of cognitive and functional decline. However, the association between IGF measures and functional and cognitive outcomes has been mixed, and the associations may vary by sex. The present study investigated the cross-sectional, sex-specific associations between serum measures total IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio, gait speed, and cognition in 1320 cognitively unimpaired participants aged 50-95 years enrolled in the Mayo Clinic Study of Aging. We used multivariable linear regression models to determine the association between IGF measures and gait speed or cognitive test performance by sex. IGF measures were not associated with cognitive or functional performance among men. Among women, higher levels of log total IGF-1 and IGFBP-3 were associated with better performance in attention, visuospatial, and global cognitive domains, independent of the gait speed. These findings suggest that among women, IGF measures are associated with cognition, and these associations are independent of function.

Trajectories of plasma IGF-1, IGFBP-3, and their ratio in the Mayo Clinic Study of Aging.

Insulin-like growth factor 1 (IGF-1) has been associated with osteoporosis, cardiovascular disease, cancer, neurodegenerative diseases, and mortality in middle and older aged adults. Cross-sectionally, IGF-1 decreases with age and levels of IGF-1 are markedly different between individuals. However, little is known about intra-individual trajectories of IGF-1. We examined baseline and serial measures of plasma total IGF-1, IGF binding protein (IGFBP)-3, and their ratio, which is a proxy for bioavailable IGF-1, among 1618 adults, aged 50-95, enrolled in the Mayo Clinic Study of Aging. At baseline, IGF-1 and IGFBP-3 were strongly correlated (r = 0.62, p < 0.001). Total IGF-1 and IGFBP-3 decreased across age, while the ratio of IGF-1/IGFBP-3 increased across age. This pattern was consistent across ages at baseline and intra-individually over an average 2.3 years follow-up (range = 10 months-5.6 years). In age-adjusted linear regression models, baseline levels of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 varied by participant characteristics (sex, BMI, gait speed), medical comorbidities (Charlson comorbidity index score, hypertension, diabetes, and cardiovascular disease), and hormone replacement therapy use in women. High interclass correlation coefficients (ICCs) suggest little intra-individual variability in levels of total IGF-1 (ICC = 0.84), IGFBP-3 (ICC = 0.88), and IGF-1/IGFBP-3 (ICC = 0.81) over time. In mixed effects models that specified age as a time scale, men showed greater decreases in total IGF-1 and IGFBP-3 with age, while more comorbidities and decreasing gait speed were associated with increasing IGFBP-3. In sex-stratified models, trajectories of total IGF-1, IGFBP-3, and IGF-1/IGFBP-3, as a function of participant demographics, health characteristics, and medical conditions, differed between men and women. These results suggest that change in levels of plasma total IGF-1, IGFBP-3, and IGF-1/IGFBP-3 are associated with demographics, health characteristics, and medical conditions, and that the trajectories of change differ by sex. Future research should consider how IGF-1 and IGFBP-3 might be useful in research or clinic, paying particular attention to how sex may impact levels as a function of demographics, health characteristics, and medical conditions.

Plasma Sphingolipids are Associated With Gait Parameters in the Mayo Clinic Study of Aging.

Background: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function. Methods: We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait. Results: Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time. Conclusions: These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.

Longitudinal Association Between Brain Amyloid-Beta and Gait in the Mayo Clinic Study of Aging.

Background: The longitudinal association between cerebral amyloid-beta (Aß) and change in gait, and whether this association is mediated by cortical thickness, has yet to be determined. Methods: We included 439 clinically normal (CN) participants, aged 50-69 years and enrolled in the Mayo Clinic Study of Aging with cerebral Aß, cortical thickness, and gait measurements. Cerebral Aß deposition was assessed by Pittsburgh Compound B (PiB)-PET in multiple regions of interest (ROIs) (ie, frontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate/precuneus, and motor). Cortical thickness was assessed on 3T MRI in corresponding ROIs. Gait parameters (gait speed, cadence, stride length, double support time, and covariance of stance time) were measured with GAITRite. Multivariate-adjusted two level structural equation models were used to examine the longitudinal association between PiB-PET, cortical thickness, and change in gait over a median 15.6 months. Results: Higher PiB-PET in all ROIs was associated with decreasing cadence and increasing double support time, and in the temporal ROI was associated with declining gait speed. In sex-stratified analyses, higher PiB-PET in all ROIs was associated with declining performance on all gait parameters among women. In contrast, among men, the only association was with higher orbitofrontal ROI PiB-PET and declining cadence. None of the associations were mediated by cortical thickness or attenuated after adjustment of baseline cognition. Conclusion: Higher PiB-PET was associated with declining gait, particularly among women in this middle-aged CN cohort, independent of cortical thickness and baseline cognitive. Elevated brain Aß may play a critical role in age-related mobility decline.

Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging.

Importance: The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood. Objectives: To determine (1) the association between plasma total tau level, cognitive decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid ß (Aß); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months. Design, Setting, and Participants: The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, Aß positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit. Exposures: Concentration of plasma total tau. Main Outcomes and Measures: Risk of MCI and dementia; global and domain-specific cognitive decline. Results: Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain Aß, both the middle (hazard ratio [HR], 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient [b] = -0.50 [0.15], P < .001) and global cognition (b = -0.27 [0.10], P = .009) at 15 months. Adjusting for elevated brain Aß did not attenuate any association. There was no interaction between plasma total tau level and brain Aß for prognosis with any outcome. Conclusions and Relevance: These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain Aß.

Longitudinal association between diabetes and cognitive decline: The National Health and Aging Trends Study.

Type II diabetes mellitus (DM) is associated with increased risk of dementia; however, few studies have examined the longitudinal association between DM and cognitive outcomes in large nationally representative cohorts. We investigated these associations in 7605 participants enrolled in the National Health and Aging Trends Study, a nationally representative prospective study of Medicare beneficiaries ≥65, from 2011 to 2015. Participants or proxy respondents reported DM and dementia diagnosis, and participants completed immediate and delayed recall word list learning tests and the Clock Drawing Test. In multivariable-adjusted generalized linear mixed models, baseline DM diagnosis was associated with decline on immediate and delayed word recall and the Clock Drawing Test. In Cox proportional hazards models, DM also predicted incident dementia in older age groups at baseline. These findings further support the notion that DM is associated with cognitive outcomes, suggesting that treatment and prevention of DM may reduce the risk of these outcomes. However, more studies are needed to better understand whether DM treatments affect this relationship.

Association between Various Brain Pathologies and Gait Disturbance.

BACKGROUND: Approximately 30% of older adults have disrupted gait. It is associated with increased risk of cognitive decline, disability, dementia, and death. Additionally, most older adults present with 1 or more neuropathologies at autopsy. Recently, there has been an effort to investigate the association between subclinical neuropathology and gait. SUMMARY: We reviewed studies that investigated the association between gait and neuropathologies. Although all pathologies reviewed were associated with gait, grey matter atrophy was most consistently linked with poorer gait performance. Studies investigating the association between white matter and gait focused primarily on total white matter. Future research using more parsed regional analysis will provide more insight into this relationship. Evidence from studies investigating neuronal activity and gait suggests that gait disruption is associated with both under- and overactivation. Additional research is needed to delineate these conflicting results. Lastly, early evidence suggests that both amyloid and tau aggregation negatively impact multiple gait parameters, but additional studies are warranted. Overall, there was substantial methodological heterogeneity and a paucity of longitudinal studies. Key Messages: Longitudinal studies mapping changes in different types of neuropathology as they relate to changes in multiple gait parameters are needed to better understand trajectories of pathology and gait.

Comparison of Gait Parameters for Predicting Cognitive Decline: The Mayo Clinic Study of Aging.

BACKGROUND: Previous studies reported that slower gait speed might predict cognitive impairment and dementing illnesses, supporting the role of gait speed as a possible subclinical marker of cognitive impairment. However, the predictive value of other gait parameters for cognitive decline is unclear. OBJECTIVE: To investigate and compare the association with, and prediction of, specific gait parameters for cognition in a population-based sample. METHODS: The analysis included 3,426 cognitively normal participants enrolled in the Mayo Clinic Study of Aging. At baseline and every 15 months (mean follow-up = 1.93 years), participants had a study coordinator evaluation, neurological examination, and a neuropsychological assessment using nine tests that covered four domains. Gait parameters were assessed with the GAITRite® instrument. General linear mixed effects models were used to compute the annualized rate of change in cognitive domain z-scores, controlling for age, sex, education, depression, comorbidities, body mass index, APOE ɛ4 allele, and visit number, and excluding individuals with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, and normal pressure hydrocephalus. RESULTS: Spatial (stride length), temporal (ambulatory time, gait speed, step count, cadence, double support time), and spatiotemporal (cadence) gait parameters, and greater intraindividual variability in stride length, swing time, and stance time were associated with a significant decline in global cognition and in specific domains including memory, executive function, visuospatial, and language. CONCLUSIONS: Spatial, temporal, and spatiotemporal measures of gait and greater variability of gait parameters were associated with and predictive of both global- and domain-specific cognitive decline.

Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic Study of Aging.

OBJECTIVES: To determine the cross-sectional association between cerebral amyloid-beta (Aß) deposition and gait. DESIGN: Cross-sectional. SETTING: Population-based cohort study in Olmsted County, MN. PARTICIPANTS: Cognitively normal individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of Aging with concurrent PiB-PET imaging and gait assessment. Participants with a history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic brain injury, or normal pressure hydrocephalus were excluded. MEASUREMENTS: PiB-PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior cingulate, posterior cingulate, and motor-specific regions of interest (ROIs). Gait parameters (speed, cadence, stride length, double support time, and intra-individual stance time variability) were measured using GAITRite® instrumentation. Linear regression models were adjusted for age, sex, body mass index, education, APOE ε4 allele, Charlson comorbidity index, and depression. In secondary analyses, we additionally adjusted for neurodegeneration (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated regions. RESULTS: In fully adjusted models including neuroimaging measures of neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower gait speed (P < .05 except for the parietal ROI), lower cadence and longer double support time (P ≤ .05 except for the motor ROI), and greater stance time variability (P < .05). In sex-stratified analyses, the association between higher PiB-PET SUVR across all ROIs and measures of gait was only present among women. CONCLUSION: PiB-PET SUVR across ROIs, independent of general measures of AD-associated neurodegeneration, is associated with poorer performance on multiple gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal studies are needed to determine whether Aß predicts gait decline in both women and men.

Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort.

INTRODUCTION: Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's disease (AD)-related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals. METHODS: Participants included 378 cognitively normal (CN) and 161 mild cognitive impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa-HD1 tau assay. RESULTS: Plasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE, higher plasma tau was associated with worse memory performance (b = -0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .018). DISCUSSION: Plasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.

Serum Adiponectin Levels, Neuroimaging, and Cognition in the Mayo Clinic Study of Aging.

BACKGROUND: Adiponectin, a protein involved in inflammatory pathways, may impact the development and progression of Alzheimer's disease (AD). Adiponectin levels have been associated with mild cognitive impairment (MCI) and AD; however, its association with Alzheimer-associated neuroimaging and cognitive outcomes is unknown. OBJECTIVE: Determine the cross-sectional association between plasma adiponectin and neuroimaging and cognitive outcomes in an older population-based sample. METHODS: Multivariable adjusted regression models were used to investigate the association between plasma adiponectin and hippocampal volume (HVa), PiB-PET, FDG PET, cortical thickness, MCI diagnosis, and neuropsychological test performance. Analyses included 535 non-demented participants aged 70 and older enrolled in the Mayo Clinic Study of Aging. RESULTS: Women had higher adiponectin than men (12,631 ng/mL versus 8,908 ng/mL, p < 0.001). Among women, higher adiponectin was associated with smaller HVa (B = -0.595; 95% CI -1.19, -0.005), poorer performance in language (B = -0.676; 95% CI -1.23, -0.121), and global cognition (B = -0.459; 95% CI -0.915, -0.002), and greater odds of a MCI diagnosis (OR = 6.23; 95% CI 1.20, 32.43). In analyses stratified by sex and elevated amyloid (PiB-PET SUVR >1.4), among women with elevated amyloid, higher adiponectin was associated with smaller HVa (B = -0.723; 95% CI -1.43, -0.014), poorer performance in memory (B = -1.02; 95% CI -1.73, -0.312), language (B = -0.896; 95% CI -1.58, -0.212), global cognition (B = -0.650; 95% CI -1.18, -0.116), and greater odds of MCI (OR = 19.34; 95% CI 2.72, 137.34). CONCLUSION: Higher plasma adiponectin was associated with neuroimaging and cognitive outcomes among women. Longitudinal analyses are necessary to determine whether higher adiponectin predicts neurodegeneration and cognitive decline.

Racial/Ethnic Differences in Insomnia Trajectories Among U.S. Older Adults.

OBJECTIVES: Insomnia is reported to be more prevalent in minority racial/ethnic groups. Little is known, however, about racial/ethnic differences in changes in insomnia severity over time, particularly among older adults. We examined racial/ethnic differences in trajectories of insomnia severity among middle-aged and older adults. DESIGN: Data were drawn from five waves of the Health and Retirement Study (2002-2010), a nationally representative longitudinal biennial survey of adults aged > 50 years. SETTING: Population-based. PARTICIPANTS: 22,252 participants from non-Hispanic white, non-Hispanic black, Hispanic, and other racial/ethnic groups. MEASUREMENTS: Participants reported the severity of four insomnia symptoms; summed scores ranged from 4 (no insomnia) to 12 (severe insomnia). We assessed change in insomnia across the five waves as a function of race/ethnicity. RESULTS: Across all participants, insomnia severity scores increased 0.19 points (95% CI: 0.14-0.24; t = 7.52; design df = 56; p < 0.001) over time after adjustment for sex, race/ethnicity, education, and baseline age. After adjusting for the number of accumulated health conditions and body mass index, this trend decreased substantially and even changed direction (B = -0.24; 95% CI: -0.29 to -0.19; t = -9.22; design df = 56; p < 0.001). The increasing trajectory was significantly more pronounced in Hispanics compared with non-Hispanic whites, even after adjustment for number of accumulated health conditions, body mass index, and number of depressive symptoms. CONCLUSIONS: Although insomnia severity increases with age-largely due to the accumulation of health conditions-this trend appears more pronounced among Hispanic older adults than in non-Hispanic whites. Further research is needed to determine the reasons for a different insomnia trajectory among Hispanics.

Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults.

Type II diabetes mellitus (DM) increases risk for cognitive decline and is associated with brain atrophy in older demented and non-demented individuals. We investigated (1) the cross-sectional association between fasting blood glucose level and cortical thickness in a sample of largely middle-aged, cognitively normal adults, and (2) whether these associations were modified by genes associated with both lipid processing and dementia. To explore possible modifications by genetic status, we investigated the interaction between blood glucose levels and the apolipoprotein E (APOE) ε4 allele and the translocase of the outer mitochondrial membrane (TOMM) 40 '523 genotype on cortical thickness. Cortical thickness measures were based on mean thickness in a subset of a priori-selected brain regions hypothesized to be vulnerable to atrophy in Alzheimer's disease (AD) (i.e., 'AD vulnerable regions'). Participants included 233 cognitively normal subjects in the BIOCARD study who had a measure of fasting blood glucose and cortical thickness measures, quantified by magnetic resonance imaging (MRI) scans. After adjustment for age, sex, race, education, depression, and medical conditions, higher blood glucose was associated with thinner parahippocampal gyri (B=-0.002; 95% CI -0.004, -0.0004) and temporal pole (B=-0.002; 95% CI -0.004, -0.0001), as well as reduced average thickness over AD vulnerable regions (B=-0.001; 95% CI -0.002, -0.0001). There was no evidence for greater cortical thinning in ε4 carriers of the APOE gene or in APOE ε3/3 individuals carrying the TOMM40 VL/VL genotypes. When individuals with glucose levels in the diabetic range (≥126mg/dL), were excluded from the analysis, the associations between glucose levels and cortical thickness were no longer significant. These findings suggest that glucose levels in the diabetic range are associated with reduced cortical thickness in AD vulnerable regions as early as middle age.

Neighborhood physical disorder, social cohesion, and insomnia: results from participants over age 50 in the Health and Retirement Study.

ABSTRACT Background: We determined the association between neighborhood socio-environmental factors and insomnia symptoms in a nationally representative sample of US adults aged >50 years. Methods: Data were analyzed from two waves (2006 and 2010) of the Health and Retirement Study using 7,231 community-dwelling participants (3,054 men and 4,177 women) in the United States. Primary predictors were neighborhood physical disorder (e.g. vandalism/graffiti, feeling safe alone after dark, and cleanliness) and social cohesion (e.g. friendliness of people, availability of help when needed, etc.); outcomes were insomnia symptoms (trouble falling asleep, night awakenings, waking too early, and feeling unrested). Results: After adjustment for age, income, race, education, sex, chronic diseases, body mass index, depressive symptoms, smoking, and alcohol consumption, each one-unit increase in neighborhood physical disorder was associated with a greater odds of trouble falling asleep (odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.04-1.14), waking too early (OR = 1.05, 95% CI: 1.00-1.10), and, in adults aged ≥69 years (adjusting for all variables above except age), feeling unrested in the morning (OR = 1.11, 95% CI: 1.02-1.22 in 2006). Each one-unit increase in lower social cohesion was associated with a greater odds of trouble falling asleep (OR = 1.06, 95% CI: 1.01-1.11) and feeling unrested (OR = 1.09, 95% CI: 1.04-1.15). Conclusions: Neighborhood-level factors of physical disorder and social cohesion are associated with insomnia symptoms in middle-aged and older adults. Neighborhood-level factors may affect sleep, and consequently health, in our aging population.

Diabetes and cognitive outcomes in a nationally representative sample: the National Health and Aging Trends Study.

BACKGROUND: The prevalence of both type II diabetes mellitus (DM) and cognitive impairment is high and increasing in older adults. We examined the extent to which DM diagnosis was associated with poorer cognitive performance and dementia diagnosis in a population-based cohort of US older adults. METHODS: We studied 7,606 participants in the National Health and Aging Trends Study, a nationally representative cohort of Medicare beneficiaries aged 65 years and older. DM and dementia diagnosis were based on self-report from participants or proxy respondents, and participants completed a word-list memory test, the Clock Drawing Test, and gave a subjective assessment of their own memory. RESULTS: In unadjusted analyses, self-reported DM diagnosis was associated with poorer immediate and delayed word recall, worse performance on the Clock Drawing Test, and poorer self-rated memory. After adjusting for demographic characteristics, body mass index, depression and anxiety symptoms, and medical conditions, DM was associated with poorer immediate and delayed word recall and poorer self-rated memory, but not with the Clock Drawing Test performance or self-reported dementia diagnosis. After excluding participants with a history of stroke, DM diagnosis was associated with poorer immediate and delayed word recall and the Clock Drawing Test performance, and poorer self-rated memory, but not with self-reported dementia diagnosis. CONCLUSIONS: In this recent representative sample of older Medicare enrollees, self-reported DM was associated with poorer cognitive test performance. Findings provide further support for DM as a potential risk factor for poor cognitive outcomes. Studies are needed that investigate whether DM treatment prevents cognitive decline.