Background: Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder with a strong genetic background. It has been reported that modifiable factors, i.e. education (E), might act as proxies for reserve capacity.

Objective: To evaluate the impact of genetic background (positive family history, FH) on reserve mechanisms, by measuring regional cerebral blood flow (rCBF) correlates in FTLD patients.

Methods: 145 FTLD patients were recruited and underwent clinical, neuropsychological, behavioral assessment, and SPECT study. The main effect of E and FH on rCBF was evaluated. To test the potential interaction between the E and rCBF in FTLD patients with or without positive FH, a difference of slope analysis in the two groups was calculated. All the analyses were controlled for disease severity (Clinical Dementia Rating Scale, FTD-CDR).

Results: A main effect of education (E+ < E-) in frontal regions was reported, and high genetic loading (FH+ < FH-) was associated with a greater bilateral temporoparietal hypoperfusion. Evaluating the relationship between E and rCBF, a greater hypoperfusion of cingulate region in FH+ as compared to FH- was observed.

Discussion: Reserve mechanisms are available also in presence of an unfavorable genetic status. However, these compensatory mechanisms are modulated by the interaction with genetic factors.