Biology subjects

Fredericks, C. A.

Publications and source records attributed to Fredericks, C. A..

4 recordsLinked to original sources

bioRxiv2024

Medial amygdalar tau is associated with anxiety symptoms in preclinical Alzheimer's disease

BACKGROUNDWhile the amygdala receives early tau deposition in Alzheimers disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms. METHODSWe examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores. RESULTSAmyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala (F(4, 442)=14.61, p=0.00045; F(4, 442)=5.83, p=0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (rs=-0.103, p=0.015). CONCLUSIONSOur findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms.

neuroscience↗

bioRxiv2022

Connectome-based predictive modeling shows sex differences in brain-based predictors of memory performance

Alzheimers disease (AD) takes a more aggressive course in women than men, with higher prevalence and faster progression. Amnestic AD specifically targets the default mode network (DMN), which subserves short-term memory; past research shows relative hyperconnectivity in the posterior DMN in aging women. Higher reliance on this network during memory tasks may contribute to womens elevated AD risk. Here, we applied connectome-based predictive modeling (CPM), a robust linear machine-learning approach, to the Lifespan Human Connectome Project-Aging (HCP-A) dataset (n=579). We sought to characterize sex-based predictors of memory performance in aging, with particular attention to the DMN. Models were evaluated using cross-validation both across the whole group and for each sex separately. Whole-group models predicted short-term memory performance with accuracies ranging from {rho}=0.21-0.45. The best-performing models were derived from an associative memory task-based scan. Sex-specific models revealed significant differences in connectome-based predictors for men and women. DMN activity contributed more to predicted memory scores in women, while within- and between-visual network activity contributed more to predicted memory scores in men. While men showed more segregation of visual networks, women showed more segregation of the DMN. We demonstrate that women and men recruit different circuitry when performing memory tasks, with women relying more on intra-DMN activity and men relying more on visual circuitry. These findings are consistent with the hypothesis that women draw more heavily upon the DMN for recollective memory, potentially contributing to womens elevated risk of AD.

neuroscience↗

bioRxiv2022

Sex differences in default mode network connectivity in healthy aging adults

Women show an increased lifetime risk of Alzheimers disease (AD) compared to men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout aging is poorly understood. We investigated sex differences in DMN connectivity over the lifespan in 595 cognitively healthy participants from the Human Connectome Project - Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and whole brain. Compared with men, women demonstrated increased connectivity with age in posterior DMN nodes and decreased connectivity in the medial prefrontal cortex. Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed increased connectivity in women from the posterior cingulate to angular gyrus and parahippocampal gyrus, which correlated with neuropsychological measures of declarative memory. Taken together, we show significant sex differences in DMN subnetworks over the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD. These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.

neuroscience↗

bioRxiv2020

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100; 60-82 yrs) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that hippocampal activity predicted cortical reinstatement strength, and these two metrics of pattern completion independently predicted retrieval success. However, increased age weakened cortical reinstatement and its relationship to memory behaviour. Critically, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

neuroscience↗