Alexandra M.V. Wennberg

Optimizing sleep in older adults: treating insomnia.

As the worlds population ages, the elevated prevalence of insomnia in older adults is a growing concern. Insomnia is characterized by difficulty falling or remaining asleep, or by non-restorative sleep, and resultant daytime dysfunction. In addition to being at elevated risk for primary insomnia, older adults are at greater risk for comorbid insomnia, which results from, or occurs in conjunction with another medical or psychiatric condition. In this review, we discuss normal changes in sleep that accompany aging, circadian rhythm changes and other factors that can contribute to late-life insomnia, useful tools for the assessment of insomnia and related problems in older people, and both non-pharmacological and pharmacological strategies for the management of insomnia and optimization of sleep in later life.

LEVELS OF TAU PROTEIN IN PLASMA ARE ASSOCIATED WITH NEURODEGENERATION AND COGNITIVE FUNCTION IN A POPULATION-BASED ELDERLY COHORT

Tau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimers disease (AD)–related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals.

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, Parkinsons 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.

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.

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.

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

To determine the cross‐sectional association between cerebral amyloid‐beta (Aβ) deposition and gait.

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.

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 &bgr; (A&bgr;); 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, A&bgr; 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 A&bgr;, 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 A&bgr; did not attenuate any association. There was no interaction between plasma total tau level and brain A&bgr; 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 A&bgr;.

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 Alzheimers 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.

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.