Mielke, Michelle M

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.

AbstractIntroductionThe clinical and pathological phenotypes of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) often overlap. We examined whether plasma lipids differed among individuals with autopsy‐confirmed Lewy Body pathology or AD pathology.MethodsWe identified four groups with available plasma 2 years before death: high (n = 12) and intermediate‐likelihood DLB (n = 14) based on the third report of the DLB consortium; dementia with Alzheimer's pathology (AD; n = 18); and cognitively normal with normal aging pathology (n = 21). Lipids were measured using ESI/MS/MS.ResultsThere were overall group differences in plasma ceramides C16:0, C18:1, C20:0, and C24:1 and monohexosylceramides C18:1 and C24:1. These lipids did not differ between the high‐likelihood DLB and AD groups, but both groups had higher levels than normals. Plasma fatty acid levels did not differ by group.DiscussionPlasma ceramides and monohexosylceramides are elevated in people with dementia with either high‐likelihood DLB or AD pathology.

Background— Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white-matter lesions 5 to 10 years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown. Methods and Results— This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study. As part of the ancillary Genetics of Microangiopathic Brain Injury (GMBI) study, a neurocognitive battery was administered; 1075 also had a brain magnetic resonance imaging. A history of a hypertensive pregnancy disorder was obtained by a self-report using a validated questionnaire. Linear models fit with generalized estimating equations were used to assess the association between hypertensive pregnancy disorders and cognition, adjusting for age, race, education, body mass index, smoking, current hypertension, hypertension duration, and family history of hypertension. Regression models for the brain magnetic resonance imaging outcomes also were adjusted for total intracranial volume. Women with histories of hypertensive pregnancy disorders performed worse on all measures of processing speed (Digital Symbol Substitution Test [mean score, 41.2 versus 43.4; P =0.005], Trail Making Test Part A [mean seconds, 45.1 versus 42.2; P =0.035], and Stroop [mean score, 173.9 versus 181.0; P =0.002]) and had smaller brain volumes compared with women with histories of normotensive pregnancies (286 versus 297; P =0.023). Conclusions— Hypertensive pregnancy disorders are associated with worse performance on tests of processing speed and smaller brain volumes decades later. Population-based studies are needed to provide critical insight as to the contribution of hypertensive pregnancies to risk of cognitive decline and dementia.

AbstractIntroductionFew studies have examined the effects of amyloid and apolipoprotein E (APOE) genotype on cognition among middle‐aged individuals.MethodsWe included 464 cognitively normal, test‐naïve, participants with Pittsburgh compound B positron emission tomography amyloid imaging, mean age of 62.7 (range, 51–71 years), enrolled in the Mayo Clinic Study of Aging. Participants completed multiple cognitive assessments, including a standard neuropsychological battery and the CogState computerized battery, over 30 months of follow‐up. Linear mixed models were used to examine the effects of amyloid and APOE genotype on baseline cognition and cognitive decline.ResultsElevated amyloid was not associated with tests of episodic memory but did predict declines on tests of executive function. APOE genotype was not associated with cognition. Among APOE ɛ4 noncarriers, higher amyloid was predictive of decline on tests of executive function and on one episodic memory test.DiscussionElevated amyloidosis and APOE genotype do not appear to exert a dramatic influence on cognition in middle age.