Brain structural indicators of ß-amyloid neuropathology.

Recent efforts demonstrated the efficacy of identifying early-stage neuropathology of Alzheimer's disease (AD) through lumbar puncture cerebrospinal fluid assessment and positron emission tomography (PET) radiotracer imaging. These methods are effective yet are invasive, expensive, and not widely accessible. We extend and improve the multiscale structural mapping (MSSM) procedure to develop structural indicators of ß-amyloid neuropathology in preclinical AD, by capturing both macrostructural and microstructural properties throughout the cerebral cortex using a structural MRI. We find that the MSSM signal is regionally altered in clear positive and negative cases of preclinical amyloid pathology (N = 220) when cortical thickness alone or hippocampal volume is not. It exhibits widespread effects of amyloid positivity across the posterior temporal, parietal, and medial prefrontal cortex, surprisingly consistent with the typical pattern of amyloid deposition. The MSSM signal is significantly correlated with amyloid PET in almost half of the cortex, much of which overlaps with regions where beta-amyloid accumulates, suggesting it could provide a regional brain 'map' that is not available from systemic markers such as plasma markers.

MRI Assessment of Cerebral White Matter Microvascular Hemodynamics Across the Adult Lifespan.

BACKGROUND: Changes in cerebral hemodynamics with aging are important for understanding age-related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter. PURPOSE: To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP-A) cohort using tract-based spatial statistics (TBSS). STUDY TYPE: Retrospective cross-sectional. POPULATION: Six hundred seventy-eight typically aging individuals (381 female), aged 36-100 years. FIELD STRENGTH/SEQUENCE: Multi-delay pseudo-continuous arterial spin labeling (ASL) and diffusion-weighted pulsed-gradient spin-echo echo planar imaging sequences at 3.0 T. ASSESSMENT: A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL-derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts. STATISTICAL TESTS: General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold-free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at PFWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at PFDR < 0.05. RESULTS: Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (PFDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA. DATA CONCLUSION: This study identified significant sex- and age-associated differences in white matter hemodynamics across tracts. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Associations between age, sex, APOE genotype, and regional vascular physiology in typically aging adults.

Altered blood flow in the human brain is characteristic of typical aging. However, numerous factors contribute to inter-individual variation in patterns of blood flow throughout the lifespan. To better understand the mechanisms behind such variation, we studied how sex and APOE genotype, a primary genetic risk factor for Alzheimer's disease (AD), influence associations between age and brain perfusion measures. We conducted a cross-sectional study of 562 participants from the Human Connectome Project - Aging (36 to >90 years of age). We found widespread associations between age and vascular parameters, where increasing age was associated with regional decreases in cerebral blood flow (CBF) and increases in arterial transit time (ATT). When grouped by sex and APOE genotype, interactions between group and age demonstrated that females had relatively greater CBF and lower ATT compared to males. Females carrying the APOEε4 allele showed the strongest association between CBF decline and ATT incline with age. This demonstrates that sex and genetic risk for AD modulate age-associated patterns of cerebral perfusion measures.

Mean Arterial Pressure and Cerebral Hemodynamics Across The Lifespan: A Cross-Sectional Study From Human Connectome Project-Aging.

BACKGROUND: Cerebral perfusion is directly affected by systemic blood pressure, which has been shown to be negatively correlated with cerebral blood flow (CBF). The impact of aging on these effects is not fully understood. PURPOSE: To determine whether the relationship between mean arterial pressure (MAP) and cerebral hemodynamics persists throughout the lifespan. STUDY TYPE: Retrospective, cross-sectional study. POPULATION: Six hundred and sixty-nine participants from the Human Connectome Project-Aging ranging between 36 and 100+ years and without a major neurological disorder. FIELD STRENGTH/SEQUENCE: Imaging data was acquired at 3.0 Tesla using a 32-channel head coil. CBF and arterial transit time (ATT) were measured by multi-delay pseudo-continuous arterial spin labeling. ASSESSMENT: The relationships between cerebral hemodynamic parameters and MAP were evaluated globally in gray and white matter and regionally using surface-based analysis in the whole group, separately within different age groups (young: <60 years; younger-old: 60-79 years; oldest-old: ≥80 years). STATISTICAL TESTS: Chi-squared, Kruskal-Wallis, ANOVA, Spearman rank correlation and linear regression models. The general linear model setup in FreeSurfer was used for surface-based analyses. P < 0.05 was considered significant. RESULTS: Globally, there was a significant negative correlation between MAP and CBF in both gray (ρ = -0.275) and white matter (ρ = -0.117). This association was most prominent in the younger-old [gray matter CBF (ß = -0.271); white matter CBF (ß = -0.241)]. In surface-based analyses, CBF exhibited a widespread significant negative association with MAP throughout the brain, whereas a limited number of regions showed significant prolongation in ATT with higher MAP. The associations between regional CBF and MAP in the younger-old showed a different topographic pattern in comparison to young subjects. DATA CONCLUSION: These observations further emphasize the importance of cardiovascular health in mid-to-late adulthood for healthy brain aging. The differences in the topographic pattern with aging indicate a spatially heterogeneous relationship between high blood pressure and CBF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.