Childhood Dementia: A Collective Clinical Approach to Advance Therapeutic Development and Care

Abstract

Childhood dementias are a group of over 100 rare and ultra-rare pediatric conditions that are clinically characterized by chronic global neurocognitive decline. This decline is associated with a progressive loss of skills and shortened life expectancy. With an estimated incidence of one in 2800 births and less than 5% of the conditions having disease-modifying therapies, the impact is profound for patients and their families. Traditional research, care, and advocacy efforts have focused on individual disorders, or groups classified by molecular pathogenesis, and this has established robust foundations for further progress and collaboration. This review describes the shared and disease-specific clinical changes contributing to childhood dementia and considers these as potential indicators of underlying pathophysiologic processes. Like adult neurodegenerative syndromes, the heterogeneous phenotypes extend beyond cognitive decline and may involve changes in eating, motor function, pain, sleep, and behavior, mediated by physiological changes in neural networks. Importantly, these physiological phenotypes are associated with significant carer stress, anxiety, and challenges in care. These phenotypes are also pertinent for the development of therapeutics and optimization of best practice management. A collective approach to childhood dementia is anticipated to identify relevant biomarkers of prognosis or therapeutic efficacy, streamline the path from preclinical studies to clinical trials, increase opportunities for the development of multiple therapeutics, and refine clinical care.