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Title: Small vessel cerebrovascular pathology identified by magnetic resonance imaging is prevalent in Alzheimer's disease and mild cognitive impairment: a potential target for intervention

Author
item SCOTT, TAMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BHADELIA, RAFEEQUE - Harvard University
item QIU, WEI QIAO - Boston University
item FOLSTEIN, MARSHAL - Tufts University
item ROSENBERG, IRWIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Alzheimer's Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/22/2018
Publication Date: 8/7/2018
Citation: Scott, T., Bhadelia, R.A., Qiu, W., Folstein, M.F., Rosenberg, I.H. 2018. Small vessel cerebrovascular pathology identified by magnetic resonance imaging is prevalent in Alzheimer's disease and mild cognitive impairment: a potential target for intervention. Journal of Alzheimer's Disease. 65(1):293-302. https://doi.org/10.3233/JAD-180366.
DOI: https://doi.org/10.3233/JAD-180366

Interpretive Summary: Alzheimer's disease can often be accompanied by changes in the small blood vessels in the brain (otherwise known as small vessel cerebrovascular disease, or SVCbD). In early Alzheimer's disease (AD), people with SVCbD are more cognitively impaired than are those individuals with AD who do not have SVCbD. Since there are currently no effective treatments for AD, SVCbD may be a valuable target for intervention to slow the onset and progression of cognitive decline in these patients. Our study looked at the prevalence and severity of SVCbD (detected with brain MRI) in 340 community-dwelling elders who had participated in the Nutrition and Memory in Elders (NAME) study, the relationship of SVCbD with AD and cognitive function, and the relationship with homocysteine levels in the blood. (Homocysteine is a marker for a disruption in a chemical process in the body for which B vitamins play a major role, and has been associated with heart disease.) We found that SVCbD was common in those participants diagnosed with AD, and was related to progression of the disease. We also found that blood homocysteine concentrations were higher in those individuals with SVCbD. In those participants with SVCbD, higher blood concentrations of homocysteine were related to poorer cognitive function and greater loss of brain cells. These findings suggest that a healthy diet may help to slow the progression of cognitive decline in AD.

Technical Abstract: Background: There is evidence that Alzheimer's disease (AD) has significant cerebrovascular etiopathogenesis. Understanding potentially modifiable risk factors for vascular disease can help design long-term intervention strategies for controlling or preventing cognitive dysfunction attributable to cerebrovascular disease. Objective: To evaluate the presence and severity of markers of cerebrovascular pathology, its relationship to diagnostic categories of dementia, including AD, and association with the metabolic biomarker homocysteine. Methods: In a cross-sectional observational study, 340 community-dwelling elders received a clinical evaluation including brain MRI and neuropsychological tests. Dementia and mild cognitive impairment (MCI) were diagnosed by consensus committee. Fasting total plasma homocysteine was measured. Statistical analyses were adjusted for demographics and cerebrovascular risk factors. Results: Nearly 25% of those diagnosed with AD had small vessel infarcts (SVI). Periventricular white matter hyperintensity (pvWMHI) was prevalent in participants with AD (61%) or MCI (amnesic 61% and non-amesic 54%, respectively). Participants with SVI and/or pvWMHI also had greater brain atrophy. Homocysteine concentrations were higher in individuals with cerebrovascular findings than in those without. In individuals with cerebrovascular disease, homocysteine was inversely related to executive function (p=0.022) and directly related to degree of brain atrophy (p=0.009). Conclusions: We demonstrated a significant prevalence of small vessel markers of cerebrovascular pathology in individuals diagnosed with AD, with a significant concurrence between cerebrovascular disease and brain and ventricular atrophy. While current research on AD has focused on amyloid-beta peptide deposition, tau-pathology, and microglial activation and inflammation, greater attention to the cerebrovascular contribution to this neurodegenerative disease presents an additional target for therapeutic prevention and intervention.