Frequency and Underlying Pathology of Pure Vascular Cognitive Impairment

Abstract

Importance: It is not clear how common pure vascular cognitive impairment (VCI) is in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies.

Objective: To identify participants without AD and other neurodegenerative pathologies and determine the extent to which cerebrovascular disease pathologies were associated with cognitive impairment.

Design, setting, and participants: This clinical pathological study included participants from 2 ongoing community-based cohorts that began enrollment in 1994 and 1997. Prior to death, participants were observed for a mean (SD) of 8.4 (5.3) years with annual assessments. From 2096 participants who died, 1799 (85.8%) underwent autopsy and 1767 had complete postmortem pathological examination data at the time of data analyses. To identify participants without neurodegenerative pathologies, we categorized them in 3 subgroups. A vascular subgroup was composed of participants without significant levels of neurodegenerative brain pathologies. A neurodegenerative subgroup was composed of participants without significant levels of cerebrovascular disease pathologies. A mixed subgroup was composed of the rest of the participants. Data were analyzed from May 2021 to July 2022.

Exposures: Brain pathology indices obtained by postmortem pathological assessments.

Main outcomes and measures: The primary outcome was cognitive impairment defined by presence of mild cognitive impairment or dementia. The secondary outcome was cognition assessed by 19 neuropsychological tests.

Results: Of 1767 included participants, 1189 (67.3%) were women, and the mean (SD) age at death was 89.4 (6.6) years. In the vascular subgroup (n = 369), cognitive impairment was present in 156 participants (42.3%) and was associated with cerebrovascular disease pathologies (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P < .001; arteriolosclerosis in basal ganglia: OR, 1.35; 95% CI, 1.04-1.76; P = .03) but not AD or other neurodegenerative pathologies, an indication of pure VCI. In mixed-effects models including all the pathologies, only macroinfarcts were associated with a faster cognitive decline rate (estimate, -0.019; SE, 0.005; P < .001) in the vascular subgroup. Further analyses identified macroinfarcts in the frontal white matter to be associated with faster cognitive decline rate when macroinfarcts of cortical and subcortical brain regions were examined in a single model.

Conclusions and relevance: In this study, pure VCI was not rare. Macroinfarcts, specifically in frontal white matter, were the main cerebrovascular disease pathologies associated with cognitive decline in pure VCI.

Figure 1.. Association of Macroinfarcts, Atherosclerosis, and Arteriolosclerosis in Basal Ganglia With Pure Vascular Cognitive Impairment

Each plot illustrates the association of age at death with probability of cognitive impairment of average women in this study (age 87 years and with 16 years of education) with different levels of macroinfarcts (A), atherosclerosis (B), and arteriolosclerosis at basal ganglia (C).

Figure 2.. Association of Macroinfarcts With Pure Vascular Cognitive Decline Prior to Death

Each plot illustrates cognitive decline trajectories of 3 average women in this study (age 87 years and with 16 years of education) with none, 1, and 2 or more macroinfarcts. Global cognition and cognitive domains scores are composite measures derived from standardized scores of 19 neuropsychological tests described in the eMethods in the Supplement.