TY - JOUR
T1 - Small vessel cerebrovascular pathology identified by magnetic resonance imaging is prevalent in Alzheimer's disease and mild cognitive impairment
T2 - A potential target for intervention
AU - Scott, Tammy M.
AU - Bhadelia, Rafeeque A.
AU - Qiu, Wei Qiao
AU - Folstein, Marshal F.
AU - Rosenberg, Irwin H.
N1 - Funding Information:
While current research on AD has focused on amyloid-β peptide deposition, tau-pathology, cell death of cholinergic neurons, and microglial activation and inflammation, attention to small vessel cerebrovascular contribution to the etiopathogenesis Supported by the USDA (agreement 58-1950-0-014), the National Institute on Aging (R01AG21790-01), and General Clinical Research Center funded by the National Center for Research Resources of the NIH, MO1-RR00054. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript. We thank Gayle Petty and the Nutrition Evaluation laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University for analytical contributions.
Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - cerebrovascular disease
KW - dementia
KW - homocysteine
KW - magnetic resonance imaging
KW - neuropsychological testing
KW - small vessel pathology
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U2 - 10.3233/JAD-180366
DO - 10.3233/JAD-180366
M3 - Article
C2 - 30040728
AN - SCOPUS:85051855491
SN - 1387-2877
VL - 65
SP - 293
EP - 302
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -