Cognitive aspects of MELAS and CARASAL

• Published in: Cerebral circulation - cognition and behavior 2022-01, Vol.3, p.100139-100139, Article 100139
• Main Authors: Canavero, I, Rifino, N, Montano, V, Pantoni, L, Gatti, L, Pollaci, G, Potenza, A, Carrozzini, T, Finsterer, J, Bersano, A
• Format: Article
• Language: English
• Subjects: CARASAL; Cerebral small vessel disease; Cognitive impairment; Heritable; MELAS; Monogenic diseases; Vascular dementia
• ISSN: 2666-2450; 2666-2450
• DOI: 10.1016/j.cccb.2022.100139

•MELAS and CARASAL have been associated with clinical evidence of cognitive impairment and should be considered as possible causes of early onset Vascular Dementia (VaD), particularly in patients with a familial history of dementia or cerebrovascular disease.•Cognitive deterioration in MELAS involves executive function, attention, language, memory, visuospatial, and motor functioning and may correlate with the total Stroke-like episodes (SLEs) lesion load.•CARASIL is characterized by late and slow cognition disorders, involving episodic memory, executive functions and facial recognition. Monogenic diseases, although rare, should be always considered in the diagnostic work up of vascular dementia (VaD), particularly in patients with early onset and a familial history of dementia or cerebrovascular disease. They include, other than CADASIL, Fabry disease, Col4A1-A2 related disorders, which are well recognized causes of VaD, other heritable diseases such as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and cathepsin-A related arteriopathy strokes and leukoencephalopathy (CARASAL). MELAS, caused by mtDNA (80% of adult cases m.3243A>G mutations) and more rarely POLG1 mutations, has minimum prevalence of 3.5/100,000. CARASAL, which is caused by mutations in the CTSA gene, has been described in about 19 patients so far. In both these two disorders cognitive features have not been fully explored and are described only in case series or families. This review paper is aimed at providing an update on the clinical manifestations, with particular focus on cognitive aspects, but also neuroradiological and genetic features of these less frequent monogenic diseases associated with VaD.