scholarly journals Cortical tau deposition follows patterns of entorhinal functional connectivity in aging

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jenna N Adams ◽  
Anne Maass ◽  
Theresa M Harrison ◽  
Suzanne L Baker ◽  
William J Jagust
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Resting State ◽  
Amyloid Β ◽  
Resting State Fmri ◽  
Aging Brain ◽  
Functional Specialization ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Neural Connections

Tau pathology first appears in the transentorhinal and anterolateral entorhinal cortex (alEC) in the aging brain. The transition to Alzheimer’s disease (AD) is hypothesized to involve amyloid-β (Aβ) facilitated tau spread through neural connections. We contrasted functional connectivity (FC) of alEC and posteromedial EC (pmEC), subregions of EC that differ in functional specialization and cortical connectivity, with the hypothesis that alEC-connected cortex would show greater tau deposition than pmEC-connected cortex. We used resting state fMRI to measure FC, and PET to measure tau and Aβ in cognitively normal older adults. Tau preferentially deposited in alEC-connected cortex compared to pmEC-connected or non-connected cortex, and stronger connectivity was associated with increased tau deposition. FC-tau relationships were present regardless of Aβ, although strengthened with Aβ. These results provide an explanation for the anatomic specificity of neocortical tau deposition in the aging brain and reveal relationships between normal aging and the evolution of AD.

scholarly journals The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Chemin Lin ◽  
Maria Ly ◽  
Helmet T. Karim ◽  
Wenjing Wei ◽  
Beth E. Snitz ◽  
...  
Keyword(s):  
Neural Networks ◽  
Older Adults ◽  
Cognitive Function ◽  
Functional Connectivity ◽  
Resting State ◽  
Clinical Symptoms ◽  
Rate Of Change ◽  
Resting State Functional Connectivity ◽  
Cognitive Changes ◽  
Cognitively Normal

Abstract Background Pathological processes contributing to Alzheimer’s disease begin decades prior to the onset of clinical symptoms. There is significant variation in cognitive changes in the presence of pathology, functional connectivity may be a marker of compensation to amyloid; however, this is not well understood. Methods We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsburgh compound B (PiB)-PET, and glucose metabolism (FDG)-PET imaging for up to 6 years. Resting-state MRI was used to estimate connectivity of seven canonical neural networks using template-based rotation. Using voxel-wise paired t-tests, we identified neural networks that displayed significant changes in connectivity across time. We investigated associations among amyloid and longitudinal changes in connectivity and cognitive function by domains. Results Left middle frontal gyrus connectivity within the memory encoding network increased over time, but the rate of change was lower with greater amyloid. This was no longer significant in an analysis where we limited the sample to only those with two time points. We found limited decline in cognitive domains overall. Greater functional connectivity was associated with better attention/processing speed and executive function (independent of time) in those with lower amyloid but was associated with worse function with greater amyloid. Conclusions Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.

scholarly journals Relationship between Stroop performance and resting state functional connectivity in cognitively normal older adults.

2013 ◽  
Vol 27 (5) ◽  
pp. 516-528 ◽  
Author(s):  
Janet M. Duchek ◽  
David A. Balota ◽  
Jewell B. Thomas ◽  
Abraham Z. Snyder ◽  
Patrick Rich ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Resting State ◽  
Resting State Functional Connectivity ◽  
Cognitively Normal

scholarly journals Networks of worry—towards a connectivity-based signature of late-life worry using higher criticism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew R. Gerlach ◽  
Helmet T. Karim ◽  
Joseph Kazan ◽  
Howard J. Aizenstein ◽  
Robert T. Krafty ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Resting State ◽  
Large Scale ◽  
Resting State Fmri ◽  
Anterior Cingulate ◽  
Resting State Functional Connectivity ◽  
Targeted Interventions ◽  
Higher Criticism ◽  
Large Scale Network

AbstractSevere worry is a complex transdiagnostic phenotype independently associated with increased morbidity, including cognitive impairment and cardiovascular diseases. We investigated the neurobiological basis of worry in older adults by analyzing resting state fMRI using a large-scale network-based approach. We collected resting fMRI on 77 participants (>50 years old) with varying worry severity. We computed region-wise connectivity across the default mode network (DMN), anterior salience network, and left executive control network. All 22,366 correlations were regressed on worry severity and adjusted for age, sex, race, education, disease burden, depression, anxiety, rumination, and neuroticism. We employed higher criticism, a second-level method of significance testing for rare and weak features, to reveal the functional connectivity patterns associated with worry. The analysis suggests that worry has a complex, yet distinct signature associated with resting state functional connectivity. Intra-connectivities and inter-connectivities of the DMN comprise the dominant contribution. The anterior cingulate, temporal lobe, and thalamus are heavily represented with overwhelmingly negative association with worry. The prefrontal regions are also strongly represented with a mix of positive and negative associations with worry. Identifying the most salient connections may be useful for targeted interventions for reducing morbidity associated with severe worry in older adults.

scholarly journals Healthy Aging Alters the Functional Connectivity of Creative Cognition in the Default Mode Network and Cerebellar Network

2021 ◽  
Vol 13 ◽  
Author(s):  
Abhishek Uday Patil ◽  
Deepa Madathil ◽  
Chih-Mao Huang
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Default Mode Network ◽  
Resting State ◽  
Brain Networks ◽  
Aging Brain ◽  
Younger Adults ◽  
Default Mode ◽  
Creative Cognition ◽  
Group Ica

Creativity is a higher-order neurocognitive process that produces unusual and unique thoughts. Behavioral and neuroimaging studies of younger adults have revealed that creative performance is the product of dynamic and spontaneous processes involving multiple cognitive functions and interactions between large-scale brain networks, including the default mode network (DMN), fronto-parietal executive control network (ECN), and salience network (SN). In this resting-state functional magnetic resonance imaging (rs-fMRI) study, group independent component analysis (group-ICA) and resting state functional connectivity (RSFC) measures were applied to examine whether and how various functional connected networks of the creative brain, particularly the default-executive and cerebro-cerebellar networks, are altered with advancing age. The group-ICA approach identified 11 major brain networks across age groups that reflected age-invariant resting-state networks. Compared with older adults, younger adults exhibited more specific and widespread dorsal network and sensorimotor network connectivity within and between the DMN, fronto-parietal ECN, and visual, auditory, and cerebellar networks associated with creativity. This outcome suggests age-specific changes in the functional connected network, particularly in the default-executive and cerebro-cerebellar networks. Our connectivity data further elucidate the critical roles of the cerebellum and cerebro-cerebellar connectivity in creativity in older adults. Furthermore, our findings provide evidence supporting the default-executive coupling hypothesis of aging and novel insights into the interactions of cerebro-cerebellar networks with creative cognition in older adults, which suggest alterations in the cognitive processes of the creative aging brain.

scholarly journals Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults

2021 ◽  
Author(s):  
Elena Rodriguez-Vieitez ◽  
Victor Montal ◽  
Jorge Sepulcre ◽  
Cristina Lois ◽  
Bernard Hanseeuw ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Decline ◽  
Structural Changes ◽  
Mean Diffusivity ◽  
Amyloid Β ◽  
Cox Proportional Hazards ◽  
Aging Brain ◽  
Clinical Progression ◽  
Cognitively Normal

AbstractNoninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer’s disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression. The study sample comprised n = 196 cognitively normal older adults (mean[SD] 72.5 [9.4] years; 114 women [58.2%]) from the Harvard Aging Brain Study. At baseline, all participants underwent structural MRI, DWI, 11C-Pittsburgh compound-B-PET, 18F-flortaucipir-PET imaging, and cognitive assessments. Longitudinal measures of Preclinical Alzheimer Cognitive Composite-5 were available for n = 186 individuals over 3.72 (1.96)-year follow-up. Prospective clinical follow-up was available for n = 163 individuals over 3.2 (1.7) years. Surface-based image analysis assessed vertex-wise relationships between cMD, global amyloid-β, and entorhinal and inferior-temporal tau. Multivariable regression, mixed effects models and Cox proportional hazards regression assessed longitudinal cognition, brain structural changes and clinical progression. Tau, but not amyloid-β, was positively associated with cMD in AD-vulnerable regions. Correcting for baseline demographics and cognition, increased cMD predicted steeper cognitive decline, which remained significant after correcting for amyloid-β, thickness, and entorhinal tau; there was a synergistic interaction between cMD and both amyloid-β and tau on cognitive slope. Regional cMD predicted hippocampal atrophy rate, independently from amyloid-β, tau, and thickness. Elevated cMD predicted progression to mild cognitive impairment. Cortical microstructure is a noninvasive biomarker that independently predicts subsequent cognitive decline, neurodegeneration and clinical progression, suggesting utility in clinical trials.

scholarly journals Functional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults

2019 ◽  
Vol 30 (3) ◽  
pp. 1974-1983
Author(s):  
Federico d’Oleire Uquillas ◽  
Heidi I L Jacobs ◽  
Aaron P Schultz ◽  
Bernard J Hanseeuw ◽  
Rachel F Buckley ◽  
...  
Keyword(s):  
Older Adults ◽  
Memory Performance ◽  
Amyloid Β ◽  
Neural Substrates ◽  
Neural Correlates ◽  
Judgments Of Learning ◽  
Aging Brain ◽  
Functional Magnetic Resonance ◽  
Tau Pathology ◽  
Brain Study

Abstract Judgments of learning (JOL) pertain to introspective metamemory processes evaluating how well information is learned. Using a functional magnetic resonance imaging (fMRI) task, we investigated the neural substrates of JOL predictions in a group of 105 cognitively unimpaired older adults from the Harvard Aging Brain Study. Associations of JOL performance and its neural correlates with amyloid-β (Aβ) and tau pathology, two proteinopathies associated with Alzheimer’s disease (AD) and aging, were also examined. We found that trials judged as learned well relative to trials judged as learned less well (high JOL > low JOL) engaged the ventromedial prefrontal cortex and precuneus, among other midline regions, in addition to bilateral hippocampi. In this cohort of older adults, greater levels of entorhinal tau deposition were associated with overestimation of memory performance and with lower fMRI signal in midline regions during predicted memory success. No associations with Aβ were found. The findings suggest that tau pathology in unimpaired older adults may play a role in altered metamemory processes. We discuss our findings in light of the hypothesis that JOLs are partially dependent on a process involving attempts to retrieve a correct answer from memory, as well as implications for clinical research investigating unawareness of memory performance (i.e., anosognosia) in patients with AD dementia.

scholarly journals Resting-State Functional Connectivity Signatures of Apathy in Community-Living Older Adults

2021 ◽  
Vol 13 ◽  
Author(s):  
Jung Yun Jang ◽  
S. Duke Han ◽  
Belinda Yew ◽  
Anna E. Blanken ◽  
Shubir Dutt ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Orbitofrontal Cortex ◽  
Resting State ◽  
Neural Mechanism ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Resting State Functional Connectivity ◽  
The Right

Apathy predicts poor outcomes in older adults, and its underlying neural mechanism needs further investigation. We examined the association between symptoms of apathy and functional connectivity (FC) in older adults without stroke or dementia. Participants included 48 individuals (mean age = 70.90) living independently in the community, who underwent resting-state fMRI and completed the Apathy Evaluation Scale (AES). Seed-to-voxel analysis (cluster-level p-FDR <0.05, voxel threshold p < 0.001) tested the association between AES scores and the whole-brain FC of brain regions involved in reward- and salience-related processing. We found that AES scores were negatively associated with FC of the right insula cortex and right anterior temporal regions (124 voxels, t = −5.10) and FC of the left orbitofrontal cortex and anterior cingulate regions (160 voxels, t = −5.45), and were positively associated with FC of the left orbitofrontal cortex and left lateral prefrontal (282 voxels, t = 4.99) and anterior prefrontal (123 voxels, t = 4.52) regions. These findings suggest that apathy in older adults may reflect disruptions in neural connectivity involved in reward- and salience-related processing.

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