Vascular factors in dementia: prevention and pathology (original) (raw)
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Stroke, 2010
Background and Purpose-White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. Methods-A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Results-Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, Pϭ0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Conclusions-Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease. (Stroke. 2010;41:554-556.
Vascular Risk Factors and Dementia: How to Move Forward?
Neurology, 2009
In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia. Neurology ® 2009;72:368-374 GLOSSARY AD ϭ Alzheimer disease; VaD ϭ vascular dementia; WMH ϭ white matter hyperintensities. Over the past 10 years, a growing body of literature, including several large population-based clinicopathologic or clinicoradiologic studies, has highlighted the important contribution of vascular risk factors (hypertension and diabetes as primary examples) in Alzheimer disease (AD). 1-4 In the Rotterdam study, one of the first large studies that called attention to this issue, dementia was associated with the presence of atherosclerosis and this association applied to subjects clinically diagnosed with vascular-type dementia as well as those with AD. 2 An association between high blood pressure and the risk of AD was also reported in other cohort studies with a 15-to 21-year follow-up. 1,3 Diabetes, a high level of cholesterol, tobacco smoking, as well as other vascular risk factors have also been associated with a higher risk of AD. 5-7 Furthermore, atrial fibrillation, hypertension, and angina have been shown to be associated with a greater rate of decline in patients with AD. 8 Apart from the occurrence of a clinical stroke, the mechanisms by which vascular factors increase the risk of AD or accelerate cognitive deterioration among patients with AD are not yet fully elucidated. Most of these factors have been shown to be associated with subcortical lesions seen on brain MRI: white matter hyperintensities (WMH), 9-12 lacunar infarctions, 13-15 or cerebral microhemorrhages. 16 There is also evidence to suggest that lowering blood pressure may stop or delay the progression of WMH. 17 The extent of WMH has been clearly linked both to cognitive impairment and the risk of incident dementia in several population-based studies. 11,18-20 Further, small, clinically silent brain infarctions appear to be at least as strong a risk for subsequent dementia 21 as larger, clinically evident strokes. 22,23 It is, however, likely that these lesions do not fully explain the impact of vascular factors on the brain and that there exist other more subtle structural changes that may have consequences related to cognition and dementia.
Vascular burden and Alzheimer disease pathologic progression
2012
Objective: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. Methods: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden ϫ time) or timevarying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. Results: Cardiovascular risk profiles were not predictive of progression in CSF  42-amyloid, [ 18 F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. Conclusion: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. Neurology ® 2012;79:1349-1355 GLOSSARY A ϭ -amyloid; AD ϭ Alzheimer disease; ADNI ϭ Alzheimer's Disease Neuroimaging Initiative; ASAD-cog ϭ Alzheimer's Disease Assessment ScaleϪCognitive Subscale; FDG ϭ [ 18 F]fluorodeoxyglucose; GEE ϭ generalized estimating equation; MCI ϭ mild cognitive impairment; MMSE ϭ Mini-Mental State Examination; NC ϭ normal cognition; WMH ϭ white matter hyperintensity. Both Alzheimer disease (AD) and vascular pathology are common in the elderly population, and multiple brain pathologic conditions account for most patients with dementia. 1 Many cardiovascular risk factors including midlife hypertension, diabetes, dyslipidemia, and smoking seem to increase the risk of AD, suggesting a vascular contribution to the etiology of AD. 2,3 Within the framework of the neurovascular unit, vascular dysfunction may reduce the clearance of -amyloid (A) via the bloodbrain barrier or indirectly increase A deposition. 4 Amyloid deposition is considered the pivotal event in the AD pathologic cascade, 5 but whether the accumulation is accelerated by vascular risks remains unclear. White matter hyperintensities (WMHs) on brain MRI reflect cardiovascular risk profiles, and greater WMH volume is associated with cerebral hypometabolism and cognitive decline. 6-8 White
CMBES Proceedings, 2021
Distinguishing Alzheimer's disease (AD) from mixed Alzheimer's and vascular dementia (VD) is a challenging task. In this study, we explored the differences between AD patients and a group with a mixed pathology of AD with cerebrovascular disease (CVD) by analyzing the volumes of several brain regions vulnerable to AD and evidenced by white matter hyper-intensities (WMHs). Moreover, we investigated the correlation between brain volumes and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores of the AD and AD-CVD groups. We collected T1-weighted Magnetization Prepared Acquisition with Gradient Echo (MPRAGE) MRI scans from 9 AD participants and 8 AD-CVD participants. Then, we performed the region of interest (ROI) analysis over the MRI data to measure the gray matter (GM) volume of the hippocampus, frontal gyrus, and precuneus as well as the cerebrospinal fluid (CSF) volume of ventricles. Also, we calculated the volume of white matter hyper-intensities (WMHs) of the whole brain and of the frontal-temporal (FT) area. The results did not show any correlation between the baseline ADAS-Cog scores of AD participants and their volumes of above-affected areas and WMHs, while in the AD-CVD group, the CSF volume in ventricles showed a high correlation with ADAS-Cog scores (Spearman's ρ = 0.714). We did not observe any statistically significant difference in these volumes between AD patients and AD-CVD group.
Investigation into the vascular contributors to dementia and the associated treatments
2023
As the average lifespan has increased, memory disorders have become a more pressing public health concern. However, dementia in the elderly population is often neglected in light of other health priorities. Therefore, expanding the knowledge surrounding the pathology of dementia will allow more informed decision-making regarding treatment within elderly and older adult populations. An important emerging avenue in dementia research is understanding the vascular contributors to dementia. This review summarizes potential causes of vascular cognitive impairment like stroke, microinfarction, hypertension, atherosclerosis, blood-brain barrier dysfunction, and cerebral amyloid angiopathy. Also, this review address treatments that target these vascular impairments that also show promising results in reducing patient's risk for and experience of dementia.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015
We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction (CVD-path), and Alzheimer's disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β=-0.61, s.e.=0.06) was four times stronger than that of AS (β=-0.15, s.e.=0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β=-0.13, s.e.=0.04). In contrast, the effects of AD pathology on global cognition (β=-0.50, s....