Christianson, Teresa J.

AbstractIntroductionRapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes.MethodsFifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed.ResultsOver 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia.DiscussionOur findings from the population‐based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies.

Objective There is a need for inexpensive noninvasive tests to identify older healthy persons at risk for Alzheimer disease (AD) for enrollment in AD prevention trials. Our objective was to examine whether abnormalities in neuroimaging measures of amyloid and neurodegeneration are correlated with odor identification (OI) in the population‐based Mayo Clinic Study of Aging. Methods Cognitively normal (CN) participants had olfactory function assessed using the Brief Smell Identification Test (B‐SIT), underwent magnetic resonance imaging (n = 829) to assess a composite AD signature cortical thickness and hippocampal volume (HVa), and underwent 11 C‐Pittsburgh compound B (n = 306) and 18 fluorodeoxyglucose (n = 305) positron emission tomography scanning to assess amyloid accumulation and brain hypometabolism, respectively. The association of neuroimaging biomarkers with OI was examined using multinomial logistic regression and simple linear regression models adjusted for potential confounders. Results Among 829 CN participants (mean age = 79.2 years; 51.5% men), 248 (29.9%) were normosmic and 78 (9.4%) had anosmia (B‐SIT score < 6). Abnormal AD signature cortical thickness and reduced HVa were associated with decreased OI as a continuous measure (slope = −0.43, 95% confidence interval [CI] = −0.76 to −0.09, p = 0.01 and slope = −0.72, 95% CI = −1.15 to −0.28, p < 0.01, respectively). Reduced HVa, decreased AD signature cortical thickness, and increased amyloid accumulation were significantly associated with increased odds of anosmia. Interpretation Our findings suggest that OI may be a noninvasive, inexpensive marker for risk stratification, for identifying participants at the preclinical stage of AD who may be at risk for cognitive impairment and eligible for inclusion in AD prevention clinical trials. These cross‐sectional findings remain to be validated prospectively. Ann Neurol 2017;81:871–882

Objectives To investigate the timing (mid‐ vs late life) of physical activity, apolipoprotein ( APO )E ε 4, 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 ( HR s) and 95% confidence intervals ( CI s) 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 ε 4 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 .

One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer’s disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23–3.64); the point estimate was further elevated for APOE ɛ 4 carriers (OR = 2.59; 1.00–6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD.