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Symptoms and age of prodromal Alzheimer’s disease in Down syndrome: a systematic review and meta-analysis

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Abstract

The diagnostic criteria for adult-onset Alzheimer’s disease (AD) in patients with Down syndrome (DS) have not been standardised. This study investigated the specific symptoms of AD in the prodromal stage of DS, the mean age at diagnosis at each stage of dementia, and the relationship between intellectual disability (ID) and dementia. PubMed, Web of Science, and Embase were searched for studies on DS, AD, early-stage disease, initial symptoms, and prodromal dementia registered between January 2012 and January 2022. We also performed a meta-analysis of the differences between the mean age at prodromal symptoms and AD diagnosis and the proportion of mild cognitive impairment in patients with mild and moderately abnormal ID. We selected 14 articles reporting the behavioural and psychological symptoms of dementia (BPSD) and memory- and language-related impairments as early symptoms of AD in patients with DS. The specific symptoms of BPSD were classified into five categories: irritability (agitation), apathy, abnormal behaviour, adaptive functioning, and sleep disturbance. The mean age at the diagnosis of prodromal symptoms and AD dementia was 52.7 and 56.2 years, respectively (mean difference, + 3.11 years; 95% CI 1.82–4.40) in the meta-analysis. The diagnosis of mild dementia tended to correlate with ID severity (odds ratio [OR], 1.38; 95% CI 0.87–2.18). The features of behaviour-variant frontotemporal dementia may be clinically confirmed in diagnosing early symptoms of DS-associated AD (DSAD). Moreover, age-appropriate cognitive assessment is important. Further studies are required to evaluate DSAD using a combination of biomarkers and ID-related data.

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Data Availability

This study analysed publicly available datasets, and the original contributions of the study are outlined in the article and/or supplementary materials. Further inquiries can be directed to the corresponding author.

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Funding

This study was supported by JSPS KAKENHI (grant number: JP23K08279).

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Authors and Affiliations

  1. Department of Clinical Genetics, Juntendo University, 2-1-1, Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan

    Eri Shimizu, Keiko Goto-Hirano & Masami Arai

  2. The Medical Center for Dementia, Juntendo Hospital, Tokyo, Japan

    Yumiko Motoi

  3. Department of Neurology, Juntendo University, Tokyo, Japan

    Nobutaka Hattori

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  1. Eri Shimizu
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  2. Keiko Goto-Hirano
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Correspondence to Keiko Goto-Hirano.

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This study was exempted from ethical review by the Juntendo University Ethical Review Committee for Medical Research in accordance with the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects.

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ES, MA, YM, and NH have no relevant financial or non-financial interests to disclose. KG obtained grants from JSPS.

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Shimizu, E., Goto-Hirano, K., Motoi, Y. et al. Symptoms and age of prodromal Alzheimer’s disease in Down syndrome: a systematic review and meta-analysis. Neurol Sci 45, 2445–2460 (2024). https://doi.org/10.1007/s10072-023-07292-9

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