Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's disease.

BACKGROUND: Cerebrovascular disease is common in Alzheimer's disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. OBJECTIVE: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. METHODS: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 +/- 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. RESULTS: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 +/- 4.5 micromol/l) were significant ly elevated compared with the AD without SBIs (11.7 +/- 4.7 micromol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 micromol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74-12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid beta-peptide(1-42) levels were not significantly correlated with pHcy levels in AD. CONCLUSION: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.

Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways.

BACKGROUND: Mild cognitive impairment (MCI) may be a heterogeneous condition rather than a uniform disease entity. OBJECTIVE: To develop reliable tools that aid in identifying patients at risk of developing Alzheimer disease (AD) among heterogeneous populations with MCI to maximize the benefits of emerging therapies for AD. DESIGN: A 2-year prospective study. SETTING: Clinical follow-up in an outpatient memory clinic. PATIENTS: Seventy-two consecutive older patients with memory complaints. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau levels, severity of periventricular and deep white matter lesions, silent brain infarction on magnetic resonance imaging, plasma homocysteine levels, apolipoprotein E genotype, and other vascular risk factors were assessed at baseline. RESULTS: Fifty-seven patients were diagnosed as having amnestic MCI. Forty-one patients with (AD-converted MCI group) or without (progressive MCI group) conversion to dementia and AD progressed over time, whereas the other 16 patients remained cognitively stable (stable MCI group). The stable MCI group was characterized by normal cerebrospinal fluid tau levels and a high grade of periventricular white matter lesions (PWMLs). The progressive MCI and AD-converted MCI groups had increased cerebrospinal fluid tau levels and low grades of PWMLs. A logistic regression model showed that age was significantly associated with developing PWMLs (P =.03; odds ratio, 1.15; 95% confidence interval, 1.0-1.3). CONCLUSIONS: Tau-related AD pathologic conditions and possibly ischemic PWMLs represent 2 major etiologies in the development of MCI, reflecting heterogeneity in the clinical progression. Because the progressive type of MCI may be a primary target of clinical trials that aim at secondary prevention of dementia, these patients should be identified by appropriate biomarkers and neuroimaging techniques.

[Diagnosing the mild cognitive impairment stage of Alzheimer's disease].

Recently, it has become important to diagnose Alzheimer's Disease (AD) at an early stage due to the development of AD therapy. Also, there is increasing recognition of a class of elderly people with complaints of memory loss but who nevertheless do not meet the criteria for dementia. "Mild cognitive impairment" (MCI) is the term used for this disorder, and amnestic MCI is highly converted to AD. In this study we evaluated the accuracy of diagnosis of amnestic MCI by cerebrospinal fluid total-tau protein (CSF/total-tau), cerebrospinal fluid amyloid beta 1-42 protein (CSF/A beta 1-42), and cerebral blood flow in the posterior cingulate cortex using SPECT. CSF/total-tau was the most appropriate to discriminate between normal cognitive individuals and those with amnestic MCI. We also evaluated the CSF/total-tau and MRI images between patients with stable MCI and those with progressive MCI, including those who converted to AD in the following two years. The stable type was characterized by normal CSF/total-tau levels and relatively high grade periventricular white matter lesions (PWML). Conversely, the progressive type was characterized by high CSF-tau levels and relatively low grade PWML. We speculate that stable MCI is due to ischemic change with in the white matter lesion, while progressive MCI may represent a previous stage of AD.