Dataset Information

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

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.

SUBMITTER: Lin C

PROVIDER: S-EPMC6945413 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Lin Chemin C Ly Maria M Karim Helmet T HT Wei Wenjing W Snitz Beth E BE Klunk William E WE Aizenstein Howard J HJ

Alzheimer's research & therapy 20200106 1

<h4>Background</h4>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.<h4>Methods</h4>We recruited 64 cognitively normal older adults who underwent neuropsychological testing and biannual magnetic resonance imaging (MRI), amyloid imaging with Pittsbu ...[more]

PMID: 31907079

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Project description:Importance:Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. Objective:To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Design, Setting, and Participants:Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ?4 (APOE?4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOE?4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n?=?25). Main Outcomes and Measures:Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). Results:The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOE?4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOE?4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95% CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (??=?3.3, partial r?=?0.4, P?=?.002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOE?4 carriers than in noncarriers. Conclusions and Relevance:We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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