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Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10160-10165. doi: 10.1073/pnas.1804641115. Epub 2018 Sep 17.

Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging.

Author information

1
Umeå Center for Functional Brain Imaging, Department of Radiation Sciences, Umeå University, 901 87 Umeå, Sweden; anna.rieckmann@umu.se.
2
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129.
3
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
4
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
5
Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
6
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
7
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
8
Department of Psychology, Harvard University, Cambridge, MA 02138.
9
Center for Brain Science, Harvard University, Cambridge, MA 02138.

Abstract

Age-related changes in striatal function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.

KEYWORDS:

aging; dopamine; functional connectivity; memory; striatum

PMID:
30224467
PMCID:
PMC6176586
[Available on 2019-04-02]
DOI:
10.1073/pnas.1804641115
[Indexed for MEDLINE]

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