Prospective Analysis of Leisure-Time Physical Activity in Midlife and Beyond and Brain Damage on MRI in Older Adults

OBJECTIVE: To test the hypothesis that greater levels of leisure-time moderate to vigorous intensity physical activity (MVPA) in midlife or late life are associated with larger gray matter volumes, less white matter disease, and fewer cerebrovascular lesions measured in late life, we utilized data from 1,604 participants enrolled in the Atherosclerosis Risk in Communities study. METHODS: Leisure-time MVPA was quantified using a past-year recall, interviewer-administered questionnaire at baseline and 25 years later and classified as none, low, middle, and high at each time point. The presence of cerebrovascular lesions, white matter hyperintensities (WMH), white matter integrity (mean fractional anisotropy [FA] and mean diffusivity [MD]), and gray matter volumes were quantified with 3T MRI in late life. The odds of cerebrovascular lesions were estimated with logistic regression. Linear regression estimated the mean differences in WMH, mean FA and MD, and gray matter volumes. RESULTS: Among 1,604 participants (mean age 53 years, 61% female, 27% Black), 550 (34%), 176 (11%), 250 (16%), and 628 (39%) reported no, low, middle, and high MVPA in midlife, respectively. Compared to no MVPA in midlife, high MVPA was associated with more intact white matter integrity in late life (mean FA difference 0.13 per SD [95% confidence interval (CI) 0.004, 0.26]; mean MD difference -0.11 per SD [95% CI -0.21, -0.004]). High MVPA in midlife was also associated with a lower odds of lacunar infarcts (odds ratio 0.68, 95% CI 0.46, 0.99). High MVPA was not associated with gray matter volumes. High MVPA compared to no MVPA in late life was associated with most brain measures. CONCLUSION: Greater levels of physical activity in midlife may protect against cerebrovascular sequelae in late life

An action for the exact string black hole

A local action is constructed describing the exact string black hole discovered by Dijkgraaf, Verlinde and Verlinde in 1992. It turns out to be a special 2D Maxwell-dilaton gravity theory, linear in curvature and field strength. Two constants of motion exist: mass M>1, determined by the level k, and U(1)-charge Q>0, determined by the value of the dilaton at the origin. ADM mass, Hawking temperature T_H \propto \sqrt{1-1/M} and Bekenstein-Hawking entropy are derived and studied in detail. Winding/momentum mode duality implies the existence of a similar action, arising from a branch ambiguity, which describes the exact string naked singularity. In the strong coupling limit the solution dual to AdS_2 is found to be the 5D Schwarzschild black hole. Some applications to black hole thermodynamics and 2D string theory are discussed and generalizations - supersymmetric extension, coupling to matter and critical collapse, quantization - are pointed out.Comment: 41 pages, 2 eps figures, dedicated to Wolfgang Kummer on occasion of his Emeritierung; v2: added ref; v3: extended discussion in sections 3.2, 3.3 and at the end of 5.3 by adding 2 pages of clarifying text; updated refs; corrected typo

[Accepted Manuscript] Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.

Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Association of common genetic variants with brain microbleeds

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed geno