Visual association pathology in preclinical Alzheimer disease.
ABSTRACT The transition from normal aging to mild cognitive impairment to Alzheimer disease (AD) is often indistinct. Imaging studies suggest early changes in posterior brain regions, including posterior temporoparietal and occipital cortex, but pathologic studies show initial changes in the medial temporal lobe with progressive neocortical involvement as cognition deteriorates. We evaluated the regional distribution of AD pathology in 41 elderly brain donors from the Framingham Heart Study who were cognitively intact, mildly impaired, or demented on the basis of probable AD. We found that 52% of the cognitively intact subjects, and all subjects with mild cognitive impairment or dementia, had dense neurofibrillary tangles (NFTs), neuropil threads, and tau-immunoreactive neurites surrounding neuritic plaques (NPs) in visual association cortex Brodmann area 19. All cognitively intact subjects with area 19 NFTs also had dense core NP and beta amyloid (Abeta) angiopathy in area 19. Area 19 pathology was occasionally present in the absence of substantial pathology in the hippocampus or entorhinal cortex and was not correlated with medial temporal lobe pathology. Dense AD pathology in area 19 is present in some cognitively intact subjects with preclinical AD. The unique metabolic, connectional, and vascular features of this region may confer enhanced vulnerability to neurodegeneration.
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ABSTRACT: Abstract We examined the progression of lexical-retrieval deficits in individuals with neuropathologically determined Alzheimer's disease (AD; n = 23) and a comparison group without criteria for AD (n = 24) to determine whether linguistic changes were a significant marker of the disease. Our participants underwent multiple administrations of a neuropsychological battery, with initial administration occurring on average 16 years prior to death. The battery included the Boston Naming Test (BNT), a letter fluency task (FAS) and written description of the Cookie Theft Picture (CTP). Repeated measures analysis revealed that the AD-group showed progressively greater decline in FAS and CTP lexical performance than the comparison group. Cross-sectional time-specific group comparisons indicated that the CTP differentiated performance between the two groups at 7-9 years prior to death and FAS and BNT only at 2-4 years. These results suggest that lexical-retrieval deficits in written discourse serve as an early indicator of AD.Clinical Linguistics & Phonetics 08/2013; DOI:10.3109/02699206.2013.815278 · 0.78 Impact Factor
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ABSTRACT: This study was to investigate the feasibility of frequency doubling technology (FDT) visual field testing in Alzheimer's disease (AD) in order to identify early biomarkers of AD in patients already diagnosed with AD and compare the findings to participants not having Alzheimer's disease. This biomarker would be useful in a battery of tests for the early identification of those with AD. It was not the intent to correlate the visual system biomarker with severity of disease, but to determine if the biomarker was present in pass or fail screening criteria. The study showed with very strong significance that the FDT can identify biomarkers of those with AD compared to an age-matched population that does not have AD. FDT is a simple test to take and administer and has been used to screen for eye and retinal diseases such as glaucoma, retinal macular degeneration, and diabetic retinopathy. The results obtained in the FDT readout are analyzed and compared to the age normative database within the system. The FDT ability to screen for AD biomarker in the visual system was significant in those with AD compared to the controls, and the deficits were not related to any ocular pathology.01/2013; 2013:989583. DOI:10.1155/2013/989583
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ABSTRACT: In recent years, the focus of research on Alzheimer's disease (AD) has shifted toward finding reliable diagnostic biomarkers that enable accurate detection of mild cognitive impairment (MCI) as well as AD. Functional magnetic resonance imaging (fMRI) has the potential to identify functional changes in the preclinical stages of AD. In addition to the cardinal deficits in memory, deficits in visuospatial cognition are pervasive in AD. Recent neurophysiological and imaging studies have revealed that changes in visuospatial perception (VSP) functions can be detected in the early stages of AD. This review highlights the scope of VSP functional alterations as a biomarker for AD. We describe the neuroanatomical regions involved in the processing of various VSP tasks, and discuss the effect of AD on these regions from a pathological as well as a functional point of view. A comprehensive synopsis of the existing fMRI literature that has assessed VSP in patients with MCI and AD has been provided. The diagnostic scope of monitoring the brain activation correlates of VSP processing in AD is discussed in terms of the key advantages of utilizing VSP-related deficits in AD for early detection and longitudinal tracking of AD.Journal of Alzheimer's disease: JAD 07/2012; 31:S117-35. DOI:10.3233/JAD-2012-120901 · 3.61 Impact Factor