Abstract Details

MCI is a clinical pre-dementia state where impaired cognitive domains (memory, executive, etc.) may predict underlying pathology (Alzheimer’s disease, AD, vs. Lewy body, LB, vs. other). Delineating neuropathological heterogeneity in MCI and their associations with neuropsychological profiles are important in identifying individuals at risk of further deterioration.

To characterize the neuropathological heterogeneity in cases with mild cognitive impairment (MCI).

Cases with a final consensus cognitive diagnosis of MCI (n= 128) prior to death were selected from the Arizona Study of Aging and Neurodegenerative disorders (AZSAND). A comparison cohort of cognitively unimpaired (n=195) were also selected. Groups were further divided into amnestic (aMCI) and non-amnestic MCI (naMCI), as well as single and multi-domain impairment. Presence and severity of neuropathology including AD, LB, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), cerebral infarcts and microinfarcts (cortical and subcortical), TAR DNA-binding protein 43 (TDP-43), and apolipoprotein E (ApoE) status were compared between MCI and cognitively unimpaired cases, as well as MCI subtypes.

When comparing MCI to cognitively unimpaired cases, plaque density, Braak AD stages, CWMR, number of microinfarcts (subcortical but not cortical), LB pathology, and TDP-43 were higher in the MCI group. When comparing to naMCI (n=31), the aMCI (n=82) group had a higher number of subcortical infarcts (p=0.012).  Within the aMCI group, those with single domain had less CWMR (p=0.001) compared to the multidomain group. In the naMCI group, those with single domain impairment had higher proportions of CAA (p=0.042), and lower LB density (p=0.019) compared to multidomain naMCI.

Vascular pathology including subcortical infarcts, CWMR and CAA appear to be commonly associated with both aMCI and naMCI. CWMR and LBs appear to be more frequent in multidomain aMCI and naMCI respectively. AD pathology was higher in MCI, but no differences were found between aMCI and naMCI.