Frailty and Mortality Outcomes in Cognitively Normal Older People: Sex Differences in a Population-Based Study

© 2016, the Authors Journal compilation. Objectives To characterize frailty in cognitively normal older adults at baseline and to investigate the relationship between frailty and mortality. Design Population-based prospective cohort study: Mayo Clinic Study of Aging. Setting Olmsted County, Minnesota. Participants Cognitively normal older persons aged 70 and older (mean age 78.8 ± 5.2, 50.2% male; N = 2,356). Measurements Frailty was assessed at baseline using a 36-item Frailty Index. Four frailty subgroups were identified based on the Frailty Index (≤0.10 (fit), 0.11-0.20 (at risk), 0.21-0.30 (frail), \u3e0.30 (frailest)). All participants underwent comprehensive clinical and cognitive assessments. The association between frailty and mortality was assessed using Cox proportional hazards models. Results The median Frailty Index was 0.17 (interquartile range 0.11-0.22). Frailty increased with age and was more common in older men than in older women. Over a median follow-up of 6.5 years (range 7 days to 8.9 years), 500 of the 2,356 participants died, including 292 men. The frailest participants had the greatest risk of death (hazard ratio (HR) = 3.91, 95% confidence interval (CI) = 2.69-5.68). The association was stronger in women (HR = 5.26, 95% CI = 2.88-9.61) than men (HR = 3.15, 95% CI = 1.98-5.02). Conclusion Baseline frailty was common, especially in older men, and increased with age. Frailty was associated with significantly greater risk of death, particularly in women. These sex differences should be considered when designing a geriatric care plan

Timing of Physical Activity, Apolipoprotein E ε4 Genotype, and Risk of Incident Mild Cognitive Impairment

© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society Objectives: To investigate the timing (mid- vs late life) of physical activity, apolipoprotein (APO)E ε4, and risk of incident mild cognitive impairment (MCI). Design: Prospective cohort study. Setting: Mayo Clinic Study of Aging (Olmsted County, MN). Participants: Cognitively normal elderly adults (N = 1,830, median age 78, 50.2% female). Measurements: Light, moderate, and vigorous physical activities in mid- and late life were assessed using a validated questionnaire. An expert consensus panel measured MCI based on published criteria. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with age as a time scale after adjusting for sex, education, medical comorbidity, and depression. Results: Light (HR = 0.58, 95% CI = 0.43–0.79) and vigorous (HR = 0.78, 95% CI = 0.63–0.97) physical activity in midlife were associated with lower risk of incident MCI. The association between moderate activity and incident MCI was not significant (HR = 0.85, 95% CI = 0.67–1.09). In late life, light (HR = 0.75, 95% CI = 0.58–0.97) and moderate (HR = 0.81, 95% CI = 0.66–0.99) but not vigorous physical activity were associated with lower risk of incident MCI. A synergistic interaction was also observed between mid- and late-life activity in reducing risk of incident MCI. Furthermore, APOE ε4 carriers who did not exercise had a higher risk of incident MCI than noncarriers who reported physical activity. Conclusion: Physical activity reduced the risk of incident MCI. Exercising in mid- and late life had an additive synergistic interaction in reducing the risk of MCI

Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: A population-based study

© 2015 American Academy of Neurology. Objective: To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI). Methods: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity. Results: Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95%CI = 1.24-3.91; test for additive interaction, p \u3c 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia. Conclusions: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia