Search

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.

In the conventional view, aging of the brain is associated with atrophy vascular abnormalities and loss of volume in hippocampus and amygdala. Cognitively, aging is associated with slowing of processing and memory loss. However, many studies of aging do not examine the cases to exclude demented people. The nutrition and memory in the homebound elderly study (NAME) excluded cases clinically diagnosed as having dementia. Cortical atrophy based on MRI ratings was significantly correlated with vascular disease, white matter hyperintensities, processing speed, and memory but not hippocampus and amygdala volume. Renal function and homocysteine were also associated with cortical atrophy but not with the cognitive variables. In conclusion, brain atrophy of aging in the absence of dementia is related to vascular disease but not hippocampal atrophy. Studies of nutritional interventions should consider using MRI atrophy rather than cognition as outcome., (© 2010 International Life Sciences Institute.)

Objective: There is a growing literature on the relationship between low serum B-vitamins, elevated homocysteine, and cognitive impairment; however, few studies have examined radiological markers of associated neuropathology in geropsychiatry inpatients. The authors examined the relationship of homocysteine, folate, and vitamin B12 with magnetic resonance imaging (MRI) markers of neuropathology., Methods: In this archival study, authors reviewed the MRIs and medical records of 34 inpatients in a geriatric psychiatry unit. Patients were selected if folate, B12, and/or homocysteine levels had been assessed and if the appropriate clinical MRIs were performed (19 men; mean age, 75 years). Patients with schizophrenia or current substance dependence were excluded. The relationships between MRI volume measures, white-matter hyperintensity (WMH) grade, and serum concentrations of folate, B12, and homocysteine were analyzed, using age-adjusted Pearson correlations., Results: Homocysteine was related to WMH grade, but not brain-volume measures. Folate was associated with hippocampus and amygdala, and negatively associated with WMH. B12 level was not statistically associated with any brain measure., Conclusions: Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups. Larger samples will be needed to assess interactions between homocysteine, micronutrients, and other neuropathology risk factors.

Background: The ratio of high amyloid-b peptide40 (Ab40) and low Ab42 in plasma predicts the risk of Alzheimer’s disease (AD) and is associated with episodic recall in depression. We thus examined the relationship between plasma Ab levels and brain volumes. Methods: Homebound elders (N¼352) who had undergone brain MRI were used. Plasma Ab1-40 and Ab1-42 were measured by ELISA. Volumes of medial temporal regions, including the amygdala and hippocampus, were manually measured. Results: Amygdala volume was associated with log10 of plasma Ab1-42 (b=+0.19, SE=0.07, p=0.005) after adjusting for AD, infarcts, white matter hyperintensities and demographics. In the absence of dementia, decreasing quartiles of plasma Ab1-42 (Mean+SD ml: Q4=4.1±0.8; Q3=3.9±0.7; Q2=3.6±0.8 and Q1=3.7±0.8, p=0.01) and increasing quartiles of plasma Ab1-40/1-42 ratio were associated with smaller amygdala volume. Those depressed subjects with a high plasma Ab1-40/1-42 ratio had smaller amygdala (Mean+SD ml: 3.3=0.8 vs. 3.6±0.8, p=0.04) and total brain volume (Mean+SD liter: 0.95±0.07 vs. 1.04=0.12, p=0.005), and had a higher rate of MCI (67 vs. 36%, p=0.02) than those with a low plasma Ab1-40/1-42 ratio. Conclusions: The combination of low plasma Ab1-42 concentration and atrophy of the medial temporal lobe structures, which regulates mood and cognition, may represent a biomarker for a prodromal stage of AD. [ABSTRACT FROM AUTHOR]