The effect of amyloid deposition on longitudinal resting-state functional connectivity in cognitively normal older adults.
Amyloid
Compensation
Connectivity
Homeostatic regulation
Longitudinal
PiB
Preclinical Alzheimer’s disease
Resting-state fMRI
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
06 01 2020
06 01 2020
Historique:
received:
06
09
2019
accepted:
23
12
2019
entrez:
8
1
2020
pubmed:
8
1
2020
medline:
12
1
2021
Statut:
epublish
Résumé
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. 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. 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. Increased functional connectivity serves to preserve cognitive function in normal aging and may fail in the presence of pathology consistent with compensatory models.
Sections du résumé
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.
Identifiants
pubmed: 31907079
doi: 10.1186/s13195-019-0573-1
pii: 10.1186/s13195-019-0573-1
pmc: PMC6945413
doi:
Substances chimiques
Amyloidogenic Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
7Subventions
Organisme : NIA NIH HHS
ID : R37 AG025516
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005133
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG025516
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG055381
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH076079
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG021885
Pays : United States
Organisme : National Institute on Aging (US)
ID : 5K23AG038479
Pays : International
Organisme : NIA NIH HHS
ID : P30 AG066468
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH019986
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG025204
Pays : United States
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