Abstract: Background: Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer’s pathophysiology (SNAP), especially in Asia. Objective: To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-β negative patients with mild amnestic type dementia. Methods: Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF Aβ levels. Neuroimaging and neuropsychological variables were analyzed. Results: Despite comparable MTA between Aβ positive and negative patients, Aβ-negative patients…had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their Aβ-positive counterparts (6.42 versus 4.19, p = 0.03). A larger proportion of Aβ-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results. Conclusion: Our findings demonstrate that MTA is associated with greater CVD burden among Aβ-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression.
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Keywords: Cerebrovascular disease, medial temporal lobe, neurodegeneration, suspected non-Alzheimer’s pathophysiology, white matter hyperintensity, young onset dementia.
Abstract: The association between cerebrovascular disease pathology (measured by white matter hyperintensities, WMH) and brain atrophy in early Alzheimer’s disease (AD) remain to be elucidated. Thus, we investigated how WMH influence neurodegeneration and cognition in prodromal and clinical AD. We examined 51 healthy controls, 35 subjects with mild cognitive impairment (MCI), and 30 AD patients. We tested how total and regional WMH is related to specific grey matter volume (GMV) reductions in MCI and AD compared to controls. Stepwise regression analysis was further performed to investigate the association of GMV and regional WMH volume with global cognition. We found that total…WMH volume was highest in AD but showed the strongest association with lower GMV in MCI. Frontal and parietal WMH had the most extensive influence on GMV loss in MCI. Additionally, parietal lobe WMH volume (but not hippocampal atrophy) was significantly associated with global cognition in MCI while smaller hippocampal volume (but not WMH volume) was associated with lower global cognition in AD. Thus, although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI. Our study thus highlights the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.
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Keywords: Alzheimer’s disease, cognition, grey matter, white matter hyperintensity