Cognitive reserve in frontotemporal degeneration

Abstract

Objective: To evaluate if cognitive reserve (CR) contributes to interindividual differences in frontal gray matter density (GMD) and executive impairment that underlie heterogeneity in the disease course of confirmed frontotemporal lobar degeneration (FTLD) pathology.Methods: Fifty-five patients with autopsy confirmation or a pathogenic mutation consistent with underlying tau (FTLD-tau) or TDP-43 (FTLD-TDP) pathology and 90 demographically comparable healthy controls were assessed with T1 MRI and neuropsychological measures (Mini-Mental State Examination, letter fluency, forward digit span, Rey complex figure, and Boston Naming Test). CR was indexed using a composite measure of education and occupation. We used t tests to identify reduced GMD in patients with FTLD relative to controls, regression analyses to relate reduced GMD to CR index, and correlations to relate regions of GMD associated with CR to performance on neuropsychological measures.Results: Patients with FTLD demonstrated impairment on neuropsychological measures. Patients with FTLD exhibited reduced bilateral frontotemporal GMD relative to controls, consistent with the known anatomic distribution of FTLD pathology. Higher CR index was associated with superior letter fluency and with GMD in right dorsolateral prefrontal cortex, orbitofrontal cortex, rostral frontal cortex, and inferior frontal gyrus. Furthermore, we found that higher GMD in frontal regions associated with CR was associated with superior letter fluency.Conclusions: Executive control and verbal ability assessed by letter fluency in FTLD is mediated in part by CR and frontal GMD. The identification of factors influencing cognitive and anatomic heterogeneity in FTLD suggests that CR should be considered in symptom detection, prognosis, and treatment. Neurology ® 2016;87:1813-1819 GLOSSARY AD 5 Alzheimer disease; ALS 5 amyotrophic lateral sclerosis; bvFTD 5 behavioral variant frontotemporal dementia; CBS 5 corticobasal syndrome; CR 5 cognitive reserve; FTD 5 frontotemporal dementia; FTLD 5 frontotemporal lobar degeneration; GM 5 gray matter; GMD 5 gray matter density; MMSE 5 Mini-Mental State Examination; PSP 5 progressive supranuclear palsy.

Longitudinal structural gray matter and white matter MRI changes in presymptomatic progranulin mutation carriers

“…Lobe-wise analysis did not reveal differences between pGRN+ and yCTL, but the subtle, focal nature of disease onset revealed itself upon voxel-wise investigation. While our work shows progressive changes in both GM and WM in pGRN+ individuals, our findings may be confounded in part by mechanisms such as cognitive reserve ( Massimo et al, 2015 ; Placek et al, 2016 ; Premi et al, 2013 ) that assist these individuals in maintaining their apparent presymptomatic status despite observed anatomic alterations. The sample size for our longitudinal evaluation of this rare mutation is small.…”

Cognitive reserve regulates the association between hearing difficulties and incident cognitive impairment evidence from a longitudinal study in China

“…Neuroimaging studies also showed that CR contributes to inter-individual differences in frontal gray matter density. Higher gray matter density in the frontal regions is associated with higher CR and executive function (Placek et al, 2016). In the current study, moderator analyses revealed that education levels and occupation complexity may be a more sensitive proxy for CR in the present sample.…”

Higher Level of Cognitive Reserve Reduces the Risk of Cognitive Difficulties in Healthy Adults

“…On the other hand, APOEε2 genotype in interaction with higher CR plays a protective role for cognitive functioning (Pettigrew et al, 2013). Similar links between genotype, CR and progressing symptoms of dementia (Placek et al, 2016) were reported in genetically determined (20-50 % of FTD cases) familial frontotemporal dementia (fFTD) (Olszewska, Lonergan, Fallon, & Lynch, 2016).…”