Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 11;102(11):e209413.
doi: 10.1212/WNL.0000000000209413. Epub 2024 May 17.

Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review

Hadassa Kwetsie  1 , Malu van Schaijk  1 , Sven Van Der Lee  1 , Dederieke Maes-Festen  1 , Leontine W Ten Hoopen  1 , Mieke M van Haelst  1 , Michael Coesmans  1 , Esther Van Den Berg  1 , Marie Claire Y De Wit  1 , Yolande Pijnenburg  1 , Eleonora Aronica  1 , Erik Boot  1 , Agnies M Van Eeghen  1
Affiliations

Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review

Hadassa Kwetsie et al. Neurology. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

A.M. Van Eeghen, L.W. Ten Hoopen, and M.Y. De Wit are members of the European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders (ERN-ITHACA). (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. PRISMA Flowchart
Figure 2
Figure 2. Overview of Study Selection and Data Extraction
Figure 3
Figure 3. Aging Trajectories of Cognitive Functioning
ID = intellectual disability, MCI = mild cognitive impairment.
Figure 4
Figure 4. Challenges and Recommendations for Dementia Diagnostics and Research in Rare Genetic Neurodevelopmental Disorders
ASM = antiseizure medication; DS = Down syndrome; ID = intellectual disability; LP = lumbar puncture; RGND = rare genetic neurodevelopmental disorder.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Nguengang Wakap S, Lambert DM, Olry A, et al. . Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet. 2020;28(2):165-173. doi:10.1038/s41431-019-0508-0 - DOI - PMC - PubMed
    1. Tsou AY, Bulova P, Capone G, et al. . Global Down Syndrome Foundation medical care guidelines for adults with Down syndrome workgroup. Medical care of adults with Down syndrome: a clinical guideline. JAMA. 2020 Oct 20;324(15):1543-1556. doi:10.1001/jama.2020.17024 - DOI - PubMed
    1. Janicki MP, Dalton AJ. Prevalence of dementia and impact on intellectual disability services. Ment Retard. 2000. Jun;38(3):276-88 doi: 10.1352/0047-6765(2000)038<0276:PODAIO>2.0.CO;2. - DOI - PubMed
    1. Van Schrojenstein Lantman-de Valk HMJ, Van Den Akker M, Maaskant MA, et al. . Prevalence and incidence of health problems in people with intellectual disability. J Intellect Disabil Res. 1997;41(1):42-51. doi:10.1111/j.1365-2788.1997.tb00675.x - DOI - PubMed
    1. Zigman WB, Schupf N, Devenny DA, et al. . Incidence and prevalence of dementia in elderly adults with mental retardation without Down syndrome. Am J Ment Retard. 2004;109(2):126-141. doi:10.1352/0895-8017(2004)109<126:IAPODI>2.0.CO;2 - DOI - PubMed

Publication types