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Available from: Bryan D James, Sep 27, 2015
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    • "Whether improved control of vascular risk factors has translated to decreased dementia risk is not known but has been suggested [18]. The most common etiology of dementia in older persons includes both mixed vascular and AD pathologies that become even more common as aging increases as both vascular and AD pathologies accumulate over time [19] [20]. "
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    ABSTRACT: Scientific evidence continues to demonstrate the linkage of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease. In December, 2013, the Alzheimer's Association, with scientific input from the National Institute of Neurological Disorders and Stroke and the National Heart, Lung and Blood Institute from the National Institutes of Health, convened scientific experts to discuss the research gaps in our understanding of how vascular factors contribute to Alzheimer's disease and related dementia. This manuscript summarizes the meeting and the resultant discussion, including an outline of next steps needed to move this area of research forward. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 12/2014; 11(6). DOI:10.1016/j.jalz.2014.10.008 · 12.41 Impact Factor
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    • "Different clinical dementia syndromes have degrees of clinico-pathological correlation, therefore if clinical diagnosis is used to estimate the accuracy of biomarkers and their cutoffs, inaccurate results may occur [13-15]. In addition, coincident neurodegenerative diseases (NDDs) and vascular pathology are common findings in subjects with AD in autopsy series [1,9,14,16-18]. However, clinical studies of dementia of the Alzheimer type (DAT) and other NDDs assign a single primary clinical diagnosis to patients. "
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    ABSTRACT: Autopsy series commonly report a high percentage of coincident pathologies in demented patients, including patients with a clinical diagnosis of dementia of the Alzheimer type (DAT). However many clinical and biomarker studies report cases with a single neurodegenerative disease. We examined multimodal biomarker correlates of the consecutive series of the first 22 Alzheimer's Disease Neuroimaging Initiative autopsies. Clinical data, neuropsychological measures, cerebrospinal fluid Aβ, total and phosphorylated tau and α-synuclein and MRI and FDG-PET scans. Clinical diagnosis was either probable DAT or Alzheimer's disease (AD)-type mild cognitive impairment (MCI) at last evaluation prior to death. All patients had a pathological diagnosis of AD, but only four had pure AD. A coincident pathological diagnosis of dementia with Lewy bodies (DLB), medial temporal lobe pathology (TDP-43 proteinopathy, argyrophilic grain disease and hippocampal sclerosis), referred to collectively here as MTL, and vascular pathology were present in 45.5%, 40.0% and 22.7% of these patients, respectively. Hallucinations were a strong predictor of coincident DLB (100% specificity) and a more severe dysexecutive profile was also a useful predictor of coincident DLB (80.0% sensitivity and 83.3% specificity). Occipital FDG-PET hypometabolism accurately classified coincident DLB (80% sensitivity and 100% specificity). Subjects with coincident MTL showed lower hippocampal volume. Biomarkers can be used to independently predict coincident AD and DLB pathology, a common finding in amnestic MCI and DAT patients. Cohorts with comprehensive neuropathological assessments and multimodal biomarkers are needed to characterize independent predictors for the different neuropathological substrates of cognitive impairment.
    10/2013; 1(1):65. DOI:10.1186/2051-5960-1-65
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    • "A recent large autopsy series demonstrated that AD plus vascular disease appears to be the most common type of mixed pathology in the oldest old. Furthermore, co-existing pathologies appear to increase risk for dementia, with proportionally greater numbers of oldest old patients with mixed pathology demonstrating dementia compared with the oldest old with single pathologies [52]. "
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    ABSTRACT: The population of oldest old, or people aged 85 and older, is growing rapidly. A better understanding of dementia in this population is thus of increasing national and global importance. In this review, we describe the major epidemiological studies, prevalence, clinical presentation, neuropathological and imaging features, risk factors, and treatment of dementia in the oldest old. Prevalence estimates for dementia among those aged 85+ ranges from 18 to 38%. The most common clinical syndromes are Alzheimer's dementia, vascular dementia, and mixed dementia from multiple etiologies. The rate of progression appears to be slower than in the younger old. Single neuropathological entities such as Alzheimer's dementia and Lewy body pathology appear to have declining relevance to cognitive decline, while mixed pathology with Alzheimer's disease, vascular disease (especially cortical microinfarcts), and hippocampal sclerosis appear to have increasing relevance. Neuroimaging data are sparse. Risk factors for dementia in the oldest old include a low level of education, poor mid-life general health, low level of physical activity, depression, and delirium, whereas apolipoprotein E genotype, late-life hypertension, hyperlipidemia, and elevated peripheral inflammatory markers appear to have less relevance. Treatment approaches require further study, but the oldest old may be more prone to negative side effects compared with younger patients and targeted therapies may be less efficacious since single pathologies are less frequent. We also highlight the limitations and challenges of research in this area, including the difficulty of defining functional decline, a necessary component for a dementia diagnosis, the lack of normative neuropsychological data, and other shortcomings inherent in existing diagnostic criteria. In summary, our understanding of dementia in the oldest old has advanced dramatically in recent years, but more research is needed, particularly among varied racial, ethnic, and socioeconomic groups, and with respect to biomarkers such as neuroimaging, modifiable risk factors, and therapy.
    Alzheimer's Research and Therapy 07/2013; 5(4):27. DOI:10.1186/alzrt181 · 3.98 Impact Factor
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