Objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients may frequently manifest apathy. The cognitive and neural mechanisms underlying apathy in CADASIL have not been assessed systematically. The aim was to investigate neuropsychological and brain morphological features associated with apathy in patients with p.R1006C in exon 19 (nucleotide change c.3016C>T) and p.G528C in exon 10 (nucleotide change c.1582 G>T) mutations of the NOTCH3 gene. Method: A total of 53 CADASIL patients (Mage ± SD, 56.6 ± 10.3; Meducation ± SD, 10.8 ± 3.7), with p.R1006C mutation or p.G528C mutation, and 20 age and education-matched healthy adults underwent an extensive assessment of cognitive functions and apathetic symptoms. All the participants underwent an magnetic resonance imaging study of the brain assessing the amount of white matter lesions and quantifying brain and gray matter volumes. Results: Apathy occurred in 24/53 patients (45.2%). Both apathetic and nonapathetic patients showed significantly poorer performance than controls in executive and memory tasks (all d > 0.8). Apathetic patients performed worse than nonapathetic patients on Trail Making Test (d = 0.61) and higher scores in apathy evaluation (d = 5.12). Morphometric analyses revealed that apathy was correlated with reduced right insula gray matter volume (r = .50). The p.R1006C mutation group exhibited a higher prevalence of apathy (φ = .34), more severe cognitive impairment, and smaller right insular volume (r = −.64) compared with p.G528C. Logistic regression identified right insular atrophy as the only predictor of apathy (OR = 1.002; p = .02). Conclusions: Apathy is frequent in patients with CADASIL p.R1006C mutation and is correlated with reduced gray matter volume of the right insula. These findings contribute to better understand the neural correlates of apathy. (PsycInfo Database Record (c) 2026 APA, all rights reserved)
Cortical correlates of apathy in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy with two different pathogenic mutations in the NOTCH3 gene
Trojano, Luigi
2026
Abstract
Objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients may frequently manifest apathy. The cognitive and neural mechanisms underlying apathy in CADASIL have not been assessed systematically. The aim was to investigate neuropsychological and brain morphological features associated with apathy in patients with p.R1006C in exon 19 (nucleotide change c.3016C>T) and p.G528C in exon 10 (nucleotide change c.1582 G>T) mutations of the NOTCH3 gene. Method: A total of 53 CADASIL patients (Mage ± SD, 56.6 ± 10.3; Meducation ± SD, 10.8 ± 3.7), with p.R1006C mutation or p.G528C mutation, and 20 age and education-matched healthy adults underwent an extensive assessment of cognitive functions and apathetic symptoms. All the participants underwent an magnetic resonance imaging study of the brain assessing the amount of white matter lesions and quantifying brain and gray matter volumes. Results: Apathy occurred in 24/53 patients (45.2%). Both apathetic and nonapathetic patients showed significantly poorer performance than controls in executive and memory tasks (all d > 0.8). Apathetic patients performed worse than nonapathetic patients on Trail Making Test (d = 0.61) and higher scores in apathy evaluation (d = 5.12). Morphometric analyses revealed that apathy was correlated with reduced right insula gray matter volume (r = .50). The p.R1006C mutation group exhibited a higher prevalence of apathy (φ = .34), more severe cognitive impairment, and smaller right insular volume (r = −.64) compared with p.G528C. Logistic regression identified right insular atrophy as the only predictor of apathy (OR = 1.002; p = .02). Conclusions: Apathy is frequent in patients with CADASIL p.R1006C mutation and is correlated with reduced gray matter volume of the right insula. These findings contribute to better understand the neural correlates of apathy. (PsycInfo Database Record (c) 2026 APA, all rights reserved)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
