title: Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study.
abstract: Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged ≥85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-β and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and α-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-β accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or α-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged ≥85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.
authors: Ageing Research Centre, Department of Neurobiology, Care Sciences, and Society, Karolinska Institute, 11330 Stockholm, Sweden. Babak.Hooshmand@ki.se
authors: Babak
authors: B
authors: Hooshmand
authors: Tuomo
authors: T
authors: Polvikoski
authors: Miia
authors: M
authors: Kivipelto
authors: Maarit
authors: M
authors: Tanskanen
authors: Liisa
authors: L
authors: Myllykangas
authors: Timo
authors: T
authors: Erkinjuntti
authors: Mira
authors: M
authors: Mäkelä
authors: Minna
authors: M
authors: Oinas
authors: Anders
authors: A
authors: Paetau
authors: Philip
authors: P
authors: Scheltens
authors: Elizabeth C W
authors: EC
authors: van Straaten
authors: Raimo
authors: R
authors: Sulkava
authors: Alina
authors: A
authors: Solomon
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000097:blood*; D018672:Community Health Planning; D003933:Diagnosis; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D051844:alpha-Synuclein; D006710:Homocysteine
keywords: Alzheimer pathology; Alzheimer’s disease; cerebrovascular pathology; elderly; homocysteine
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