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:ObjectiveTo understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults.MethodA total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS). The authors evaluated continuous PiB binding as a predictor of GDS score or GDS cluster, calculated as total scores and mean scores for three GDS item clusters (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years; mean=3.8 years) in separate mixed-effects models with backward elimination. Initial predictors included PiB binding, age, sex, Hollingshead score, American National Adult Reading Test (AMNART) score, apolipoprotein E ε4 status, depression history, and their interactions with time.ResultsHigher PiB binding predicted accelerated rates of increase in GDS score over time, adjusting for depression history. Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores, adjusting for depression history and the AMNART score-by-time interaction. In a post hoc model estimating anxiety scores without concentration disturbance items, the PiB binding-by-time interaction remained significant.ConclusionsHigher amyloid beta burden was associated with increasing anxious-depressive symptoms over time in cognitively normal older individuals. Prior depression history was related to higher but not worsening symptom ratings. These results suggest a direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease.

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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