Visual Performance and Cortical Atrophy in Vision-Related Brain Regions Differ Between Older Adults with (or at Risk for) Alzheimer’s Disease

2021 ◽  
pp. 1-24
Author(s):  
Sana Rehan ◽  
Nathalie Giroud ◽  
Faisal Al-Yawer ◽  
Walter Wittich ◽  
Natalie Phillips

Background: Visual impairment is associated with deficits in cognitive function and risk for cognitive decline and Alzheimer’s disease (AD). Objective: The purpose of this study was to characterize the degree of visual impairment and explore the association thereof with cortical atrophy in brain regions associated with visual processing in individuals with (or at risk for) AD. Methods: Using the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) dataset, we analyzed vision and brain imaging data from three diagnostic groups: individuals with subjective cognitive decline (SCD; N = 35), mild cognitive impairment (MCI; N = 74), and mild AD (N = 30). We used ANCOVAs to determine whether performance on reading acuity and contrast sensitivity tests differed across diagnostic groups. Hierarchical regression analyses were applied to determine whether visual performance predicted gray matter volume for vision-related regions of interest above and beyond group membership. Results: The AD group performed significantly worse on reading acuity (F(2,138) = 4.12, p <  0.01, ω 2 = 0.04) compared to the SCD group and on contrast sensitivity (F(2,138) = 7.6, p <  0.01, ω 2 = 0.09) compared to the SCD and MCI groups, which did not differ from each other. Visual performance was associated with volume in some vision-related structures beyond clinical diagnosis. Conclusion: Our findings demonstrate poor visual performance in AD and that both group membership and visual performance are predictors of cortical pathology, consistent with the idea that atrophy in visual areas and pathways contributes to the functional vision deficits observed in AD.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Céline H. De Jager ◽  
Charles C. White ◽  
David A. Bennett ◽  
Yiyi Ma

AbstractAccumulating evidence has suggested that the molecular transcriptional mechanism contributes to Alzheimer’s disease (AD) and its endophenotypes of cognitive decline and neuropathological traits, β-amyloid (Aβ) and phosphorylated tangles (TAU). However, it is unknown what is the impact of the AD risk factors, personality characteristics assessed by the NEO Five-Factor Inventory, on the human brain’s transcriptome. Using postmortem human brain samples from 466 subjects, we found that neuroticism has a significant overall impact on the brain transcriptome (omnibus P = 0.005) but not the other four personality characteristics. Focused on those cognitive decline related gene co-expressed modules, neuroticism has nominally significant associations (P < 0.05) with four neuronal modules, which are more related to PHFtau than Aβ across all eight brain regions. Furthermore, the effect of neuroticism on cognitive decline and AD might be mediated through the expression of module 7 and TAU pathology (P = 0.008). To conclude, neuroticism has a broad impact on the transcriptome of human brains, and its effect on cognitive decline and AD may be mediated through gene transcription programs related to TAU pathology.


2018 ◽  
Vol 18 (5-6) ◽  
pp. 233-238
Author(s):  
Frederic Sampedro ◽  
Juan Marín-Lahoz ◽  
Saul Martínez-Horta ◽  
Javier Pagonabarraga ◽  
Jaime Kulisevsky

The role of cerebrospinal fluid (CSF) biomarkers such as CSF α-synuclein and CSF tau in predicting cognitive decline in Parkinson’s disease (PD) continues to be inconsistent. Here, using a cohort of de novo PD patients with preserved cognition from the Parkinson’s Progression Markers Initiative (PPMI), we show that the SNCA rs356181 single nucleotide polymorphism (SNP) modulates the effect of these CSF biomarkers on cortical thinning. Depending on this SNP’s genotype, cortical atrophy was associated with either higher or lower CSF biomarker levels. Additionally, this SNP modified age-related atrophy. Importantly, the integrity of the brain regions where this phenomenon was observed correlated with cognitive measures. These results suggest that this genetic variation of the gene encoding the α-synuclein protein, known to be involved in the development of PD, also interferes in its subsequent neurodegeneration. Overall, our findings could shed light on the so far incongruent association of common CSF biomarkers with cognitive decline in PD.


2015 ◽  
Vol 11 (7S_Part_6) ◽  
pp. P274-P274 ◽  
Author(s):  
Keir X.X. Yong ◽  
Catherine Holloway ◽  
Amelia Carton ◽  
Biao Yang ◽  
Tatsuto Suzuki ◽  
...  

2021 ◽  
Author(s):  
Cherie Strikwerda-Brown ◽  
Hazal Ozlen ◽  
Alexa Pichet Binette ◽  
Marianne Chapleau ◽  
Natalie Marchant ◽  
...  

Mindfulness, defined as the ability to engage in non-judgmental awareness of the present moment, has been associated with an array of health benefits. Mindfulness may also represent a protective factor for Alzheimer's disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk of AD dementia. Measures of trait mindfulness, longitudinal cognitive assessments, and AB- and tau- positron emission tomography (PET) scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and (1) cognitive decline, (2) AB, and (3) tau. Higher levels of trait mindfulness, particularly mindful nonjudgment, were associated with less cognitive decline, AB, and tau. Trait mindfulness may represent a psychological protective factor for AD dementia.


2017 ◽  
Vol 28 (7) ◽  
pp. 705-714 ◽  
Author(s):  
Wafa Jaroudi ◽  
Julia Garami ◽  
Sandra Garrido ◽  
Michael Hornberger ◽  
Szabolcs Keri ◽  
...  

AbstractThere are many factors that strongly influence the aetiology, development, and progression of cognitive decline in old age, mild cognitive impairment (MCI), and Alzheimer’s disease (AD). These factors include not only different personality traits and moods but also lifestyle patterns (e.g. exercise and diet) and awareness levels that lead to cognitive decline in old age. In this review, we discuss how personality traits, mood states, and lifestyle impact brain and behaviour in older adults. Specifically, our review shows that these lifestyle and personality factors affect several brain regions, including the hippocampus, a region key for memory that is affected by cognitive decline in old age as well as AD. Accordingly, appropriate recommendations are presented in this review to assist individuals in decreasing chances of MCI, dementia, AD, and associated symptoms.


2006 ◽  
Vol 14 (7S_Part_11) ◽  
pp. P632-P634
Author(s):  
Heather L. Shouel ◽  
Rebecca L. Koscik ◽  
Lindsay R. Clark ◽  
Sara Elizabeth Berman ◽  
Brad T. Christian ◽  
...  

2018 ◽  
Vol 115 (6) ◽  
pp. E1289-E1298 ◽  
Author(s):  
Rachel E. Bennett ◽  
Ashley B. Robbins ◽  
Miwei Hu ◽  
Xinrui Cao ◽  
Rebecca A. Betensky ◽  
...  

Mixed pathology, with both Alzheimer’s disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer’s disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain’s microvasculature.


2020 ◽  
Vol 30 (5) ◽  
pp. 2948-2960 ◽  
Author(s):  
Nicholas M Vogt ◽  
Jack F Hunt ◽  
Nagesh Adluru ◽  
Douglas C Dean ◽  
Sterling C Johnson ◽  
...  

Abstract In Alzheimer’s disease (AD), neurodegenerative processes are ongoing for years prior to the time that cortical atrophy can be reliably detected using conventional neuroimaging techniques. Recent advances in diffusion-weighted imaging have provided new techniques to study neural microstructure, which may provide additional information regarding neurodegeneration. In this study, we used neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion model, in order to investigate cortical microstructure along the clinical continuum of mild cognitive impairment (MCI) and AD dementia. Using gray matter-based spatial statistics (GBSS), we demonstrated that neurite density index (NDI) was significantly lower throughout temporal and parietal cortical regions in MCI, while both NDI and orientation dispersion index (ODI) were lower throughout parietal, temporal, and frontal regions in AD dementia. In follow-up ROI analyses comparing microstructure and cortical thickness (derived from T1-weighted MRI) within the same brain regions, differences in NODDI metrics remained, even after controlling for cortical thickness. Moreover, for participants with MCI, gray matter NDI—but not cortical thickness—was lower in temporal, parietal, and posterior cingulate regions. Taken together, our results highlight the utility of NODDI metrics in detecting cortical microstructural degeneration that occurs prior to measurable macrostructural changes and overt clinical dementia.


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