Small Vessel Cerebrovascular Pathology Identified by Magnetic Resonance Imaging Is Prevalent in Alzheimer’s Disease and Mild Cognitive Impairment: A Potential Target for Intervention

Article type: Research Article

Authors: Scott, Tammy M.^{a; b; *} | Bhadelia, Rafeeque A.^c | Qiu, Wei Qiao^d | Folstein, Marshal F.^b | Rosenberg, Irwin H.^{a; b; e; *}

Affiliations: [a] Friedman School of Nutrition Science and Policy, Boston, MA, USA | [b] Tufts University School of Medicine, Boston, MA, USA | [c] Harvard Medical School, Boston, MA, USA | [d] Boston University School of Medicine, Boston, MA, USA | [e] USDA Jean Mayer Human Nutrition Research Center on Aging, Boston, MA, USA

Correspondence: [*] Correspondence to: Tammy M. Scott, PhD, 711 Washington Street, Boston, MA 02111, USA. Tel.: +1 617 556 3356; E-mails: [email protected]. and Irwin H. Rosenberg, MD, [email protected].

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-amnesic 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-βpeptide 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.

Keywords: Aging, Alzheimer’s disease, cerebrovascular disease, dementia, homocysteine, magnetic resonance imaging, neuropsychological testing, small vessel pathology

DOI: 10.3233/JAD-180366

Journal: Journal of Alzheimer's Disease, vol. 65, no. 1, pp. 293-302, 2018