Visual Association Pathology in Preclinical Alzheimer Disease
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.
[Show abstract] [Hide abstract] ABSTRACT: Recent proposals of diagnostic criteria within the healthy aging-Alzheimer's disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role. Considering this background, we investigated the role of cognitive reserve, cognitive performance in neuropsychological testing, hippocampal volumes, APOE genotype, and magnetoencephalography power sources to predict the conversion to AD in a sample of 33 MCI patients. MCIs were followed up during a 2-year period and divided into two subgroups according to their outcome: The "stable" MCI group (sMCI, 21 subjects) and the "progressive" MCI group (pMCI, 12 subjects). Baseline multifactorial information was submitted to a hierarchical logistic regression analysis to build a predictive model of conversion to AD. Results indicated that the combination of left hippocampal volume, occipital cortex theta power, and clock drawing copy subtest scores predicted conversion to AD with a 100% of sensitivity and 94.7% of specificity. According to these results it might be suggested that anatomical, cognitive, and neurophysiological markers may be considered as "first order" predictors of progression to AD, while APOE or cognitive reserve proxies might play a more secondary role.0Comments 0Citations
- "According to this process, the dominant alpha activity over occipital cortex is progressively substituted by a rhythm within the low-frequency range . Chiaramonti et al.  calculated the centroid of the conventional EEG bands in a group of mild and moderate AD patients, and reported that such " substitution " process was associated with disease severity (for more information on the implication of occipital pathology in AD see McKee et al. ). Now we prove that OCC theta power survived in a hierarchical selection process where multiple markers were included, suggesting that it provided with information that significantly improved the sensitivity of the model. "
[Show abstract] [Hide abstract] ABSTRACT: The present study explored whether the optic flow deficit in Alzheimer’s disease (AD) reported in the literature transfers to different types of optic flow, in particular, one that specifies collision impacts with upcoming surfaces, with a special focus on the effect of retinal eccentricity. Displays simulated observer movement over a ground plane toward obstacles lying in the observer’s path. Optical expansion was modulated by varying τ˙. The visual field was masked either centrally (peripheral vision) or peripherally (central vision) using masks ranging from 10° to 30° in diameter in steps of 10°. Participants were asked to indicate whether their approach would result in “collision” or “no collision” with the obstacles. Results showed that AD patients’ sensitivity to τ˙ was severely compromised, not only for central vision but also for peripheral vision, compared to age- and education-matched elderly controls. The results demonstrated that AD patients’ optic flow deficit is not limited to radial optic flow but includes also the optical pattern engendered by τ˙. Further deterioration in the capacity to extract τ˙ to determine potential collisions in conjunction with the inability to extract heading information from radial optic flow would exacerbate AD patients’ difficulties in navigation and visuospatial orientation.0Comments 0Citations
- "Taken together, the present results demonstrate that AD patients' optic flow deficit is not limited to radial optic flow but extends as well to the optical pattern engendered by ˙ τ and the capacity to perceive impending collision impacts. Pathological changes in the posterior parietal cortical areas are suspected to cause the optic flow deficits (Hof and Morrison, 1994; Duffy et al., 2004; McKee et al., 2006; Mapstone et al., 2008). Degeneration of neurons in MSTd that respond selectively to optic flow components such as expansion/contraction, rotation, translation, or a combination of these (Saito et al., 1986; Duffy and Wurtz, 1991a,b, 1997; Duffy, 1998) would certainly disable the capacity to perform the spatio-temporal integration needed to extract a global pattern, such as the FOE or ˙ τ , from optic flow. "
- "Because of the dense connections with other brain regions, the retrosplenial cortex is involved in various cognitive functions, including episodic memory, navigation, imagination, future planning and switching between egocentric and allocentric viewpoints (Vann et al., 2009). This might explain why not only the medial temporal lobe regions are affected in early AD, but that dysfunctions in the medial parietal regions are also important for predicting AD and understanding the pathophysiology of AD (Jacobs et al., 2012; McKee et al., 2006; Villain et al., 2010a Villain et al., , 2010b). In fact, disconnection between ventral and dorsal pathways (Chetelat et al., 2010; Desikan et al., 2010; Salat et al., 2010) as well as reduced white matter integrity in the cingulum has been found in early AD patients (Chua et al., 2008; Damoiseaux and Greicius, 2009; Rose et al., 2000; Villain et al., 2010b; Zhang et al., 2007). "