Plasma homocysteine, Alzheimer and cerebrovascular pathology: a population-based autopsy study
2013 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 136, 2707-2716 p.Article in journal (Refereed) Published
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 epsilon 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-beta 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 alpha-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-beta 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 alpha-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged epsilon 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.
Place, publisher, year, edition, pages
2013. Vol. 136, 2707-2716 p.
homocysteine, Alzheimer's disease, Alzheimer pathology, cerebrovascular pathology, elderly
IdentifiersURN: urn:nbn:se:su:diva-94179DOI: 10.1093/brain/awt206ISI: 000323965100011OAI: oai:DiVA.org:su-94179DiVA: diva2:652606
Academy of Finland 48173; 120676; 251645; 117458; 129395; EVO 5772720; Paivikki and Sakari Sohlberg Foundation; Helsinki University Central Hospital competitive research fund (EVO); Maud Kuistila Foundation; Alzheimer Foundation; Saastamoinen Foundation; Sigrid Juselius Foundation; Helsingin Sanomat Centennial Foundation; Neurological Foundation; Helsinki University Central Hospital (Finland); Karolinska Institute; Swedish Research Council for Medical Research (Vetenskapsradet); Strategic Research Program in Epidemiology (SFO) at Karolinska Institutet; Loo och Hans Östermans stiftelse; Stohnes Stiftelse; Gamla Tjänarinnor Foundation; Stiftelsen Dementia; Alzheimerfonden; Demensfonden (Sweden); EU 211696; National Institute of Health (USA) 2013-10-012013-09-302013-10-01Bibliographically approved