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: 3.8). 07/2006; 65(6):621-30. DOI: 10.1097/00005072-200606000-00010
Source: PubMed


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 · 2.08 Impact Factor
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    • "arietal region under high executive demands , and this increased activation was associated with poorer task performance . This may reflect reduced , but not impaired , efficiency of parietal lobe functions in resolving response competition . Dysfunction in the parietal region has been shown in early AD in both postmortem ( Braak and Braak , 1996 ; McKee et al . , 2006 ) and neuroimaging ( Buckner et al . , 2005 ; Jacobs et al . , 2012b ) studies . In early AD or mild cognitive impair - ment , fMRI studies have revealed either compensatory activation or functional loss in this region ( Bokde et al . , 2008 , 2010 ; Jacobs et al . , 2012a ; Prvulovic et al . , 2002 ; Sperling et al . , 2010 ; Vannini e"
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    ABSTRACT: Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.
    Neurobiology of aging 12/2013; 35(6). DOI:10.1016/j.neurobiolaging.2013.12.008 · 5.01 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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