Application of an amyloid and tau classification system in subcortical vascular cognitive impairment patients.

OBJECTIVE: To apply an AT (Aß/tau) classification system to subcortical vascular cognitive impairment (SVCI) patients following recently developed biomarker-based criteria of Alzheimer's disease (AD), and to investigate its clinical significance. METHODS: We recruited 60 SVCI patients who underwent the neuropsychological tests, brain MRI, and 18F-florbetaben and 18F-AV1451 PET at baseline. As a control group, we further recruited 27 patients with AD cognitive impairment (ADCI; eight Aß PET-positive AD dementia and 19 amnestic mild cognitive impairment). ADCI and SVCI patients were classified as having normal or abnormal Aß (A-/A+) and tau (T-/T+) based on PET results. Across the three SVCI groups (A-, A+T-, and A+T+SVCI), we compared longitudinal changes in cognition, hippocampal volume (HV), and cortical thickness using linear mixed models. RESULTS: Among SVCI patients, 33 (55%), 20 (33.3%), and seven (11.7%) patients were A-, A+T-, and A+T+, respectively. The frequency of T+ was lower in A+SVCI (7/27, 25.9%) than in A+ADCI (14/20, 70.0%, p = 0.003) which suggested that cerebral small vessel disease affected cognitive impairments independently of A+. A+T-SVCI had steeper cognitive decline than A-SVCI. A+T+SVCI also showed steeper cognitive decline than A+T-SVCI. Also, A+T-SVCI had steeper decrease in HV than A-SVCI, while cortical thinning did not differ between the two groups. A+T+SVCI had greater global cortical thinning compared with A+T-SVCI, while declines in HV did not differ between the two groups. CONCLUSION: This study showed that the AT system successfully characterized SVCI patients, suggesting that the AT system may be usefully applied in a research framework for clinically diagnosed SVCI.

Association between APOE ε2 and Aß burden in patients with Alzheimer- and vascular-type cognitive impairment.

OBJECTIVE: To investigate the association between APOE genotype and ß-amyloid (Aß) burden, as measured by PET in patients with subcortical vascular cognitive impairment (SVCI) and those with Alzheimer disease-related cognitive impairment (ADCI). METHODS: This was a cross-sectional study of 310 patients with SVCI and 999 with ADCI. To evaluate the effects of APOE genotype or diagnostic group on Aß positivity, we performed multivariate logistic regression analyses. Further distinctive underlying features of latent subgroups were examined by employing a latent class cluster analysis approach. RESULTS: In comparison with ε3 homozygotes, in the ADCI group, ε2 carriers showed a lower frequency of Aß positivity (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.23-0.79), while in the SVCI group, ε2 carriers showed a higher frequency of Aß positivity (OR 2.26, 95% CI 1.02-5.01). In particular, we observed an interaction effect of ε2 carrier status and diagnostic group on Aß positivity (OR 5.12, 95% CI 1.93-13.56), in that relative to ε3 homozygotes, there were more Aß-positive ε2 carriers in the SVCI group than in the ADCI group. We also identified latent subgroups of Aß-positive APOE ε2 carriers with SVCI and Aß-positive APOE ε4 carriers with ADCI. CONCLUSIONS: Our findings suggest that APOE ε2 is distinctly associated with Aß deposition in patients with SVCI and those with ADCI. Our findings further suggest that there is a distinctive subgroup of Aß-positive APOE ε2 carriers with SVCI among patients with cognitive impairment.

Distinct Brain Regions in Physiological and Pathological Brain Aging.

BACKGROUND: Studying structural brain aging is important to understand age-related pathologies, as well as to identify the early manifestations of the Alzheimer's disease (AD) continuum. In this study, we investigated the long-term trajectory of physiological and pathological brain aging in a large number of participants ranging from the 50s to over 80 years of age. OBJECTIVE: To explore the distinct brain regions that distinguish pathological brain aging from physiological brain aging using sophisticated measurements of cortical thickness. METHODS: A total of 2,823 cognitively normal (CN) individuals and 2,675 patients with AD continuum [874 with subjective memory impairment (SMI), 954 with amnestic mild cognitive impairment (aMCI), and 847 with AD dementia] who underwent a high-resolution 3.0-tesla MRI were included in this study. To investigate pathological brain aging, we further classified patients with aMCI and AD according to the severity of cognitive impairment. Cortical thickness was measured using a surface-based method. Multiple linear regression analyses were performed to evaluate age, diagnostic groups, and cortical thickness. RESULTS: Aging extensively affected cortical thickness not only in CN individuals but also in AD continuum patients; however, the precuneus and inferior temporal regions were relatively preserved against age-related cortical thinning. Compared to CN individuals, AD continuum patients including those with SMI showed a decreased cortical thickness in the perisylvian region. However, widespread cortical thinning including the precuneus and inferior temporal regions were found from the late-stage aMCI to the moderate to severe AD. Unlike the other age groups, AD continuum patients aged over 80 years showed prominent cortical thinning in the medial temporal region with relative sparing of the precuneus. CONCLUSION: Our findings suggested that the precuneus and inferior temporal regions are the key regions in distinguishing between physiological and pathological brain aging. Attempts to differentiate age-related pathology from physiological brain aging at a very early stage would be important in terms of establishing new strategies for preventing accelerated pathological brain aging.