Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center.
BACKGROUND
Epidemiologic studies have implicated cerebrovascular disease and its antecedents as risk factors for Alzheimer disease (AD). Cerebral atherosclerosis or strokes may increase the deposition of neuritic plaques or the formation of neurofibrillary tangles. Alternatively, they may simply hasten the age at onset of disease, or increase the severity of disease symptoms. This investigation examined the association between cerebrovascular disease and the pathologic manifestations of AD in an autopsy series.


METHODS
This was a cross-sectional study using data from the United States National Alzheimer's Coordinating Center database. The primary analysis included 1,054 individuals with clinical information and semiquantitative neuropathologic measurements: 921 had AD as the primary neuropathologic diagnosis and 133 were considered neuropathologically normal.


RESULTS
Overall, 9% of the individuals had clinical history of stroke during life, but 33% had evidence of cerebral infarcts at postmortem. There was no association between neuritic plaques or neurofibrillary tangles, the primary neuropathologic manifestations of AD, with either clinical history of stroke or the presence of cerebral infarcts at postmortem. The authors did find a higher frequency of neuritic plaques and neurofibrillary tangles with increased amyloid angiopathy. Neither plaques nor tangles were associated with small vessel cerebrovascular disease, arteriosclerosis. However, the presence of large-vessel cerebrovascular disease, or atherosclerosis, was strongly associated with an increased frequency of neuritic plaques.


CONCLUSIONS
Atherosclerotic cerebrovascular disease may have a role in the pathogenesis of Alzheimer disease, because of a strong association with frequent neuritic plaques.
Honig
Lawrence S
LS
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, the Gertrude H. Sergievsky Center, and the Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA. lh456@columbia.edu
Kukull
Walter
W
Mayeux
Richard
R
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000453:epidemiology / Q000473:pathology; D015897:Comorbidity; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D015140:Dementia, Vascular / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000150:complications / Q000453:epidemiology* / Q000473:pathology; D008297:Male; D016874:Neurofibrillary Tangles; D058225:Plaque, Amyloid; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D053327:Apolipoprotein E4; D001057:Apolipoproteins E