Measures are needed that identify persons that will develop Alzheimer's disease in order to target them for preventative interventions. There is evidence from animal, pathological and imaging studies that disruption of white matter occurs in the course of Alzheimer's disease and may be an early event. Prior studies have suggested that late-myelinating regions or white matter connecting limbic structures are particularly susceptible to degradation. Persons destined to develop the disease by virtue of fully penetrant genetic alterations (familial Alzheimer's disease or FAD) provide a model in which early and even presymptomatic changes of the disease may be identified. In this study we performed diffusion tensor imaging (DTI) on 2 demented and 21 subjects at-risk for inheriting an FAD mutation. We compared global and localized fractional anisotropy (FA) measures in white matter between FAD mutation carriers and non-carriers in the preclinical (clinical dementia rating <1, n = 20) and presymptomatic (clinical dementia rating = 0, n = 15) stages of the disease. There were no significant differences between mutation carriers and non-carriers with regard to absolute age, age relative to the typical age of disease diagnosis in their family, gender or Mini-Mental Status Examination Score. Among preclinical FAD mutation carriers (n = 12), mean whole brain white-matter FA (P = 0.045), FA of the columns of the fornix (P = 0.012), area of the perforant pathways bilaterally (right side: P = 0.028, left side: P = 0.027) and left orbitofrontal lobe (P = 0.024) were decreased relative to that of non-carriers (n = 8). We also found that FA in the columns of the fornix (P = 0.008) and left orbitofrontal lobe white matter (P = 0.045) were decreased in the eight presymptomatic mutation carriers compared to seven non-carriers. Logistic regression demonstrated that FA of the columns of the fornix was a better predictor of mutation status than was cross-sectional area of the fornix, global mean white-matter FA and left frontal lobe white-matter FA. In a linear regression analysis, white-matter volume (P = 0.002), hippocampal volume (P = 0.023) and mutation status (P = 0.032) significantly predicted fornix FA. We conclude that FA is decreased in the white matter in preclinical and even presymptomatic FAD mutation carriers, particularly in the late-myelinating tracts connecting limbic structures. Decreased FA in of the columns of the fornix is particularly robust in early FAD and may provide a biomarker for early disease in sporadic Alzheimer's disease.

Purpose To examine the potential benefits of life-long aerobic exercise on brain health, in particular cerebrovascular function. Materials and Methods Ten Masters Athletes (MA) (7 males/3 females; 74.5±5.8 yrs.) and ten sedentary elderly individuals (SE) (8 males/2 females; 75.4±5.6 yrs.) were recruited, and baseline Cerebral Blood Flow (CBF) and Cerebral Vascular Reactivity (CVR) to CO2 were measured on a 3 Tesla MRI scanner. Nine sedentary young subjects were also recruited to serve as a control group to verify the age-effect. Results When compared to the SE group, MA showed higher CBF in posterior cingulate cortex/precuneus, which are key regions of the default-mode-network and are known to be highly sensitive to age and dementia. CVR in the MA brain were paradoxically lower than that in SE. This effect was present throughout the brain. Within the MA group, individuals with higher Vo2max had an even lower CVR, suggesting a dose-response relationship. Conclusion Life-long aerobic exercise preserved blood supply in the brain’s default-mode-network against age-related degradation. On the other hand, its impact on cerebral vascular system seems to be characterized by a dampening of CO2 reactivity, possibly because of desensitization effects due to a higher lifetime exposure.

Background White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. Methods Ten Masters athletes (3 females, age=72.2±5.3yrs, endurance training>15yrs) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5±4.3yrs) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyper intensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). Results After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=−0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. Conclusions These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults.