Abstract
Multiple pathological processes are common in those with dementia and can affect clinical presentations. This study defined the extent of multiple pathological processes at autopsy in a well-characterized dementia clinic population and determined their impact on cognitive deficits. Forty-five cases from the Canadian Collaborative Cohort of Related Dementia (ACCORD) were prospectively assigned one primary clinical diagnosis and up to one secondary clinical diagnosis. Neuropathological examination followed a uniform protocol including mandatory semiquantitative assessment of a wide range of pathological changes. Multiple significant pathologies were identified in 21 cases (46.7%) including 19 cases with two cases with three pathological diagnoses. The pathological diagnoses in these mixed cases included Alzheimer disease (AD) ( n = 18), dementia with Lewy Bodies (DLB) ( n = 9, eight also with AD), frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) ( n = 10, eight with coexisting AD), cerebrovascular disease (CVD) ( n = 5, three cases with coexisting AD) and progressive supranuclear palsy (PSP) ( n = 1, also with CVD and FTLD-TDP). Only two cases with multiple pathological diagnoses were all recognized in the clinical diagnoses. Additional pathology of uncertain significance in 24 cases included vascular lesions, argyrophilic grains and hippocampal sclerosis. Patients with multiple pathologies were older and their baseline MMSE score higher at presentation.
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