Visual Association Pathology in Preclinical Alzheimer Disease

Department of Neurology and Pathology, Boston University School of Medicine, Bedford Veterans Administration Medical Center, MA 01730, USA.
Journal of Neuropathology and Experimental Neurology (Impact Factor: 4.37). 07/2006; 65(6):621-30. DOI: 10.1097/00005072-200606000-00010
Source: PubMed

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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    • "These visual association areas of the brain include the lingual gyrus and cuneus. At autopsy, patients with MCI present with AD pathology in the visual association cortex (McKee et al., 2006). Despite evidence that brain abnormalities are present in visual association areas in early stages of the disease, few studies have focused on regions associated with visual processing in MCI. "
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    ABSTRACT: Objective: Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer's disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. Method: Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored <26 were defined as "probable MCI" while those who scored ≥26 were labeled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus, and all four lobes were compared using multivariate analysis of variance (MANOVA). Regression analyses examined the relationship between DTI indices and total MoCA score. Results: Results revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine, and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. Conclusions: Results indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer's disease and anterior brain aging patterns.
    Journal of Clinical and Experimental Neuropsychology 12/2014; 37(1):1-9. DOI:10.1080/13803395.2014.985636 · 2.16 Impact Factor
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    • "AD is the most common age-related degenerative process affecting neural tissue, primarily brain. One of the early sites of AD damage is the brain's visual association area, Brodmann area 19, with loss of cells and neuronal connections [11]. FDT testing identifies cell death and loss of neuronal connections within the visual pathway [12]. "
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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.
    09/2013; 2013:989583. DOI:10.1155/2013/989583
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    • "All pathological examinations were performed by a single neuropathologist (AM) who was completely blinded to participants' clinical status. Details of the neuropathological procedures are described in McKee et al. (2006). Briefly, one cerebral and one cerebellar hemisphere were snap frozen at À80 C, while the remaining tissue was fixed in 4% periodate-lysine-paraformaldehyde (PLP) at 4 C for at least 4 weeks. "
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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; 27(12). DOI:10.3109/02699206.2013.815278 · 0.78 Impact Factor
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