Cognitive aspects of MELAS and CARASAL

Area of Science:

• Neurology
• Genetics
• Vascular Dementia Research

Background:

• Monogenic diseases are rare but crucial in diagnosing vascular dementia (VaD), particularly with early onset or family history.
• While CADASIL, Fabry disease, and Col4A1-A2 disorders are known causes, MELAS and CARASAL are less frequently recognized contributors to VaD.
• Cognitive aspects of MELAS and CARASAL are not fully understood, often limited to case series.

Purpose of the Study:

• To review and update the understanding of less common monogenic diseases associated with VaD.
• To focus on the cognitive, neuroradiological, and genetic manifestations of MELAS and CARASAL.
• To highlight the importance of considering these rare genetic disorders in VaD diagnostics.

Main Methods:

• Literature review of monogenic diseases linked to vascular dementia.
• Synthesis of clinical, cognitive, neuroradiological, and genetic data.
• Focus on mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and cathepsin-A related arteriopathy strokes and leukoencephalopathy (CARASAL).

Main Results:

• MELAS, caused by mtDNA mutations (e.g., m.3243A>G) or POLG1 mutations, has a prevalence of at least 3.5/100,000.
• CARASAL, caused by CTSA gene mutations, has been reported in approximately 19 patients.
• Cognitive deficits in MELAS and CARASAL are not comprehensively studied but are present.

Conclusions:

• Monogenic diseases, including MELAS and CARASAL, warrant consideration in the differential diagnosis of VaD.
• Further research is needed to fully elucidate the cognitive profiles associated with MELAS and CARASAL.
• Early identification of these genetic disorders can inform diagnosis and management of VaD.