Among non-motor symptoms of Parkinson disease (PD), cognitive impairment substantially reduces patients’daily living activities and quality of life. The risk factors are still poorly known: some demographic and clinical variables (older age, longer disease duration, severity of parkinsonian motor symptoms) are positively associated with cognitive decline and dementia in PD; 1 and abnormal accumulation of α-synuclein in Lewy bodies plays a pathogenic role 2. Heterozygous glucocerebrosidase (GBA) gene mutations are also strong risk factors for synucleopathies, including PD (accounting for 4-5% of sporadic cases) 3 and dementia with Lewy bodies (LBD) 4. There is also evidence that GBA mutations increase the neocortical accumulation of Lewy bodies 5 leading to more frequent and more severe cognitive impairment 5, 6 as compared to PD patients without mutations. PD patients with GBA mutations may also show more severe neuropsychiatric symptoms (anxiety, sleep and eating disorders, depression, apathy), as compared to patients with sporadic PD without GBA mutations 6. Spread of Lewy body pathology to limbic and visual associative cortical areas is probably related to the occurrence of neuropsychiatric features observed in LBD 7.
- parkinson disease