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

Premi, Enrico, Gazzina, Stefano, Bozzali, Marco, Archetti, Silvana, Alberici, Antonella, Cercignani, Mara, Bianchetti, Angelo, Gasparotti, Roberto, Turla, Marinella, Caltagirone, Carlo, Padovani, Alessandro and Borroni, Barbara (2013) Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages. PLoS ONE, 8 (9). e74762. ISSN 1932-6203

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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+).


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.


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.


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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Patricia Butler
Date Deposited: 27 Nov 2015 11:29
Last Modified: 28 Jul 2017 23:53

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