Characterization of risk factors for vascular dementia: the Honolulu-Asia Aging Study.
ABSTRACT The Honolulu Heart Program (HHP) is a prospective study of heart disease and stroke that has accumulated risk factor data on a cohort of 8,006 Japanese American men since the study began in 1965. A recent examination of the cohort identified all patients with vascular dementia (VaD) using the criteria of the California Alzheimer's Disease Diagnostic and Treatment Center.
To characterize patients with VaD by stroke subtype and to investigate risk factors for VaD in a cohort of Japanese American men, aged 71 to 93, living in Hawaii and participating in the HHP.
Sixty-eight men with VaD were compared with 3,335 men without dementia or stroke (NSND). Men with VaD were also compared with 106 men with stroke who were not demented (SND). Candidate risk factors were measured prospectively.
Of the 68 men with VaD there were 34 (50%) whose VaD was attributed to small vessel infarcts, 16 (23%) whose VaD was related to large vessel infarcts, and 11 (16%) with both large and small vessel infarcts. The remainder could not be classified. In a multivariate logistic regression model for VaD compared with NSND containing variables found to be associated with VaD in a univariate analysis, age (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.13 to 1.27), coronary heart disease (OR 2.50, 95% CI 1.35 to 4.62), and 1-hour postprandial glucose (OR 1.41, 95% CI 1.06 to 1.88) remained significantly predictive of VaD, whereas preference for a Western diet (OR 0.54, 95% CI 0.30 to 0.98) as opposed to an Oriental or mixed diet and use of supplementary vitamin E (OR 0.32, 95% CI 0.12 to 0.82) were protective. A similar model for the comparison of men with VaD and SND revealed age (OR 1.24, 95% CI 1.14 to 1.35) was predictive of VaD, whereas preference for a Western diet (OR 0.43, 95% CI 0.22 to 0.86) was protective.
The most common stroke subtype associated with VaD was lacunar stroke. Age and traditional vascular risk factors are important contributors to the development of VaD in late life. The antioxidant vitamin E and presently unknown factors related to a Western diet as opposed to an Oriental diet may be protective against developing VaD.
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ABSTRACT: Despite the fact that vascular dementia (VaD) represents the seconding leading cause of dementia in the USA, behind only Alzheimer's disease (AD), there remains a lack of consensus on the pathological criteria required for diagnosis of this disease. A number of clinical diagnostic criteria exist but are poorly validated and inconsistently applied. It is clear that vascular risk factors play an important role in the etiology of VaD, including hypertension, stroke, diabetes, and atherosclerosis. Vascular risk factors may increase the risk for VaD by promoting inflammation, cerebral vascular disease, white matter lesions, and hippocampal sclerosis. Because vascular risk factors seem to impart a high degree of risk for conferring VaD, it seems logical that the apolipoprotein E (APOE) status of individuals may be important. APOE plays a critical role in transporting cholesterol in and out of the CNS and in AD it is known that harboring the APOE allele increases the risk of AD perhaps due to the improper functioning of this protein. The purpose of this review is to examine the important pathological features and risk factors for VaD and to provide a critical assessment of the current literature regarding whether or not apoE4 also confers disease risk in VaD. The preponderance of data suggests that harboring one or both APOE4 alleles elevates the risk for VaD, but not to the same extent as found in AD.
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ABSTRACT: Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles (NFTs), blood vessels, and reactive astrocytes. Labeling occurred in VaD cases that had confirmed APOE genotypes of 3/3, 3/4, and 4/4, with respect to NFTs, staining of the nApoECF co-localized with PHF-1 and was predominantly localized to large, stellate neurons in layer II of the entorhinal cortex. Quantitative analysis indicated that approximately 38.4% of all identified NFTs contained the amino-terminal fragment of apoE. Collectively, these data support a role for the proteolytic cleavage of apoE in the VaD and support previous reports that APOE polymorphism is significantly associated with susceptibility in this disease.International journal of clinical and experimental pathology 01/2014; 7(3):938-47. · 1.78 Impact Factor
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ABSTRACT: Coronary heart disease (CHD) has been linked with cognitive decline and dementia in several studies. CHD is strongly associated with blood pressure, but it is not clear how blood pressure levels or changes in blood pressure over time affect the relation between CHD and dementia-related pathology. The aim of this study was to investigate relations between CHD and cortical thickness, gray matter volume and white matter lesion (WML) volume on MRI, considering CHD duration and blood pressure levels from midlife to three decades later. The study population included 69 elderly at risk of dementia who participated in the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. CAIDE participants were examined in midlife, re-examined 21 years later, and then after additionally 7 years (in total up to 30 years follow-up). MRIs from the second re-examination were used to calculate cortical thickness, gray matter and WML volume. CHD diagnoses were obtained from the Finnish Hospital Discharge Register. Linear regression analyses were adjusted for age, sex, follow-up time and scanner type, and additionally total intracranial volume in GM volume analyses. Adding diabetes, cholesterol or smoking to the models did not influence the results. CHD was associated with lower thickness in multiple regions, and lower total gray matter volume, particularly in people with longer disease duration (>10 years). Associations between CHD, cortical thickness and gray matter volume were strongest in people with CHD and hypertension in midlife, and those with CHD and declining blood pressure after midlife. No association was found between CHD and WML volumes. Based on these results, long-term CHD seems to have detrimental effects on brain gray matter tissue, and these effects are influenced by blood pressure levels and their changes over time.PLoS ONE 10/2014; 9(10):e109250. DOI:10.1371/journal.pone.0109250 · 3.53 Impact Factor