title: Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study.
abstract: Cerebral blood flow (CBF) velocity is decreased in patients with Alzheimer's disease. It is being debated whether this reflects diminished demand because of advanced neurodegeneration or that cerebral hypoperfusion contributes to dementia. We examined the relation of CBF velocity as measured with transcranial Doppler with dementia and markers of incipient dementia (ie, cognitive decline and hippocampal and amygdalar atrophy on magnetic resonance imaging) in 1,730 participants of the Rotterdam Study aged 55 years and older. Cognitive decline in the 6.5 years preceding CBF velocity measurement was assessed with repeated Mini-Mental State Examinations in nondemented subjects (n = 1,716). Hippocampal and amygdalar volumes were assessed in a subset of 170 nondemented subjects. Subjects with greater CBF velocity were less likely to have dementia. Furthermore, in nondemented subjects, greater CBF velocity was related to significantly less cognitive decline over the preceding period (odds ratio per standard deviation increase in mean CBF 0.74 [95% confidence interval, 0.58-0.98]) and larger hippocampal and amygdalar volumes. A low CBF is associated with dementia, but also with markers of incipient dementia. Although we cannot exclude that this is caused by preclinical neurodegeneration leading to hypoperfusion, it does suggest that cerebral hypoperfusion precedes and possibly contributes to onset of clinical dementia.
authors.affiliation: Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Ruitenberg
authors.forename: Tom
authors.initials: T
authors.lastname: den Heijer
authors.forename: Stef L M
authors.initials: SL
authors.lastname: Bakker
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D000679:Amygdala / Q000098:blood supply / Q000473:pathology; D001284:Atrophy; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009426:Netherlands; D017585:Ultrasonography, Doppler, Transcranial