Nature versus nurture in frontotemporal lobar degeneration: the interaction of genetic background and education on brain damage.

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.