Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review
Hadassa Kwetsie1, Malu van Schaijk1, Sven Van Der Lee1
1From Emma's Children's Hospital (H.K., A.M.V.E.), University of Amsterdam; Advisium (H.K., E.B., A.M.V.E.), 's Heeren Loo Zorggroep, Amersfoort; Department on Aging (M.S.), Netherlands Institute of Mental Health and Addiction (Trimbos Institute), Utrecht; Alzheimer Center Amsterdam (S.V.D.L., Y.P.), Amsterdam University Medical Center; Section Genomics of Neurodegenerative Diseases and Aging (S.V.D.L.), Department of Human Genetics Amsterdam UMC; Intellectual Disability Medicine (D.M.-F.), Department of General Practice, Erasmus MC, University Medical Center Rotterdam; ENCORE Expertise Center for Neurocognitive Disorders and Department of Pediatric Neurology (L.W.T.H., M.C.Y.D.W.), Sophia Children's Hospital, Erasmus MC University Medical Center Rotterdam; Erasmus School of Health Policy & Management (L.W.T.H.), Erasmus University Rotterdam; Department of Clinical Genetics (M.M.H.); Department of Human Genetics (M.M.H.), Amsterdam UMC, University of Amsterdam; Emma Center for Personalized Medicine (M.M.H., A.M.V.E.), Amsterdam University Medical Centers; Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam; Department of Neurology and Alzheimer Center Erasmus MC (E.V.D.B.), Erasmus MC University Medical Center, Rotterdam; Amsterdam Neuroscience (Y.P.), Neurodegeneration; Department of (Neuro)Pathology, Amsterdam Neuroscience (E.A.), Amsterdam UMC, University of Amsterdam; Stichting Epilepsie Instellingen Nederland (SEIN) (E.A.), Heemstede, The Netherlands; The Dalglish Family 22q Clinic (E.B.), University Health Network, Toronto, Canada; and Department of Psychiatry and Neuropsychology (E.B.), Maastricht University, Maastricht University, The Netherlands.
Background And Objectives:
Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs.
Methods:
A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template.
Results:
The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders.
Discussion:
Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.
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