Are There Interactions Between Vascular Brain Disease, Amyloid Deposition, and Dementia?

Abstract & Commentary

By Michael Lin, MD, PhD, Assistant Professor of Neurology and Neurosciences, Weill Cornell Medical College. Dr. Lin reports no financial relationships relevant to this field of study.

Synopsis: In a study of the elderly who are normal or have mild cognitive impairment, vascular brain disease and brain amyloid deposition appear to be independent risks for dementia.

Source: Marchant NL, et al. The aging brain and cognition. Contribution of vascular injury and a-beta to mild cognitive dysfunction JAMA Neurol 2013;70:488-495.

Alzheimer’s disease (AD) and vascular brain injury (VBI) are the leading causes of dementia in aging, with AD considered to be the most common cause. However, AD and VBI frequently co-occur, and vascular risk factors are also risk factors for AD. To assess the relationship between AD and VBI, Marchant and colleagues used amyloid (Pittsburgh B, PiB) PET to assess the burden of amyloid deposition and MRI to assess the burden of VBI (infarcts and white matter disease). Findings were correlated with performance on a cognitive test battery. There were 30 subjects with normal cognition (mean age = 77.1), 24 subjects with mild cognitive impairment (mean age = 78), and seven subjects with mild dementia (mean age = 79.8).

Overall, 56% of subjects had at least one infarct on MRI, and 48% were PiB-positive. VBI and amyloid were independent factors; the presence of an infarct did not increase the likelihood of PiB-positivity, and there was no relationship between white matter hyperintensity and global PiB index. In multivariate regressions, including demographic variables and measures of VBI and amyloid, infarction in cortical and deep gray matter was associated with decreased performance on tests of verbal memory and executive functioning. In contrast, neither amyloid nor white matter hyperintensity were significant predictors of cognition.

These data suggest a more prominent role for vascular disease in cognitive decline with aging. Other recent literature also points in the same direction. For example, Westover et al showed that finding even one microinfarct on routine neuropathologic examination suggests the presence of hundreds of microinfarcts throughout the rest of the brain.1

Commentary

The lack of correlation between amyloid PET imaging and cognition is not surprising. It has been known for some time that plaque is not the best pathologic correlate of cognitive decline in AD. Amyloid is thought to be an early, initiating event in AD pathogenesis, and more downstream events, such as tangle formation or synapse loss, correlate better with loss of cognition. Thus, studies focused on amyloid may underestimate the contribution of AD pathology to dementia.

Nonetheless, this paper emphasizes the importance of vascular disease in cognitive health. Since vascular risk factors are treatable, this may be the most important intervention to reduce the risk of dementia in the population. Moreover, even in subjects with AD, treatment of vascular risk factors is associated with slower cognitive decline.2 Counseling on vascular risk factors should be a standard part of every memory disorders clinic visit.

References

1. Westover MB, et al. Estimating cerebral microinfarct burden from autopsy samples. Neurology 2013;80:1365-1369.

2. Deschaintre Y, et al. Treatment of vascular risk factors is associated with slower decline in Alzheimer disease. Neurology 2009;73:674-680.