Mona Al Banna, MB BCh, Msc(Res)

Lamar M, Leurgans S, Kapasi A, Barnes LL, Boyle PA, Bennett DA, Arfanakis K, Schneider JA. Complex Profiles of Cerebrovascular Disease Pathologies in the Aging Brain and Their Relationship With Cognitive Decline. Stroke. 2021.

Neurodegenerative disease with concurrent cerebrovascular disease (CVD) is associated with poorer long-term outcomes and increased functional dependency. Studies suggest that the co-existence of neurodegenerative pathologies and cerebrovascular pathologies ranges from 33-75%. However, little is known about the most common frequencies of cerebrovascular disease pathology types and the combinations of cerebrovascular pathologies that are encountered with dementia. The authors of this study set out to identify CVD frequencies and combinations in neurodegenerative disease and their association with cognitive domains affected.

The authors examined 32 possible CVD combinations by looking at three types of vessel disease (arteriolosclerosis/small vessel disease, atherosclerosis and CAA) and two types of tissue injury (macro and microinfarcts). The study participants were those in prospective clinicopathological cohort studies of aging (the Religious Orders Study, the Rush Memory and Aging Project and the Minority Aging Research Study). Postmortem samples were obtained from 1528 decedents, and 1474 participants had relevant data for the purposes of this study. Both cerebrovascular and neurodegenerative pathologies were evaluated for post-mortem via a scoring system. For cognitive evaluation, a global composite cognitive function score was derived from performance on 19 cognitive tests. Cognitive domains evaluated included perceptual speed, visuospatial abilities, processing speed and episodic, semantic and working memory. Mixed-effect models were used to adjust for demographics, neuropathologies and time before death.

The authors found that the mean age at death was 89 years, and participants averaged 16.2 years of education. The most common single cerebrovascular profile was CAA, and the most common combination profile was arteriolosclerosis combined with atherosclerosis and macroinfarcts. Overall, mixed CVD profiles were more common than single CVD profiles — an expected finding given the prevalence of mixed profiles in our cerebrovascular disease population. Outside of age at death (with those with CVD neuropathology being two years older at time of death), there were no other differences in participant characteristics in those with and without CVD neuropathology. However, those with CVD neuropathology scored lower on global cognition and all composite measures of cognition. Those with evidence of mixed CVD pathology also had faster rates of decline in global cognition and all composite cognitive measures.

This study was of interest in several different ways. First, it uniquely examined mixed patterns of cerebrovascular disease in relation to cognitive decline and dementia rather than looking at single cerebrovascular profiles alone. A mixed pattern profile likely reflects clinical practice more realistically, and, therefore, the results should be interpreted in this context. Second, it emphasizes that mixed profiles that are more strongly associated with faster decline and more severe impairment in various cognitive domains. This is another factor that should be taken into evaluation in clinical practice especially given that, at times, crude cognitive evaluations done in the clinical setting lack sensitivity in capturing mild cognitive impairment. Therefore, there should be a lower threshold in further cognitive and neuropsychologic evaluation for those with mixed CVD profiles.

In sum, this study indicates that vessel disease is a key contributor to cognitive aging — a statement that cannot be understated. The future goal is facilitation of vascular biomarkers that may enable more selective clinical trials to offer timely diagnosis, relevant targets, and early intervention for cognitive decline in the setting of CVD and dementia. This study outlines that CVD and cerebrovascular cognitive impairment is not a uniform disease entity and is rather a more complex neuropathological process as it relates to brain behavior relationships. There is still much more to be explored regarding the interplay of cognition and cerebrovascular function.