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Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages

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posted on 2023-06-08, 21:09 authored by Enrico Premi, Stefano Gazzina, Marco Bozzali, Silvana Archetti, Antonella Alberici, Mara Cercignani, Angelo Bianchetti, Roberto Gasparotti, Marinella Turla, Carlo Caltagirone, Alessandro Padovani, Barbara Borroni
OBJECTIVE Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+). METHODS Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages.

History

Publication status

  • Published

File Version

  • Published version

Journal

PLoS ONE

ISSN

1932-6203

Publisher

Public LIbrary of Science

Issue

9

Volume

8

Article number

e74762

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-11-27

First Open Access (FOA) Date

2015-11-27

First Compliant Deposit (FCD) Date

2015-11-27

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