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. 2026 Feb;22(2):e71156.
doi: 10.1002/alz.71156.

Factors impacting survival in individuals with Down syndrome-associated Alzheimer's disease

Bessy Benejam  1   2 , Mary McCarron  3   4 , María Carmona-Iragui  1   2   5 , Pamela Dunne  4 , Lucia Maure-Blesa  1   5   6 , Miren Altuna  7   8 , Javier Arranz  1   9 , Isabel Barroeta  1   5 , Alexandre Bejanin  1   5 , Laura Del Hoyo Soriano  1   5 , Susana Fernández  2 , Sandra Giménez  1   5   9 , Alberto Lleó  1   5 , Louise Lynch  3 , Philip McCallion  10 , Niamh Mulryan  4 , Lucia Pertierra  1 , Anne-Sophie Rebillat  11 , Íñigo Rodríguez-Baz  1   5 , Aida Sanjuan Hernández  1 , Lídia Vaqué-Alcázar  1   12   13 , Laura Videla  1   2   5 , Andrew Wormald  3 , Juan Fortea  1   2   5 , Eimear McGlinchey  3   14
Affiliations

Factors impacting survival in individuals with Down syndrome-associated Alzheimer's disease

Bessy Benejam et al. Alzheimers Dement. 2026 Feb.

Abstract

Introduction: Adults with Down syndrome (DS) are at high risk for Alzheimer's disease (AD), the leading cause of death in this population. Survival in DS after AD diagnosis appears shorter than in sporadic AD; however, the factors influencing survival remain poorly understood.

Methods: We analyzed 157 adults with DS from Spain and Ireland who died of AD between 2012 and 2024. Clinical, genetic, and care predictors were examined using Kaplan-Meier curves and Cox regression.

Results: Mean survival after AD diagnosis was 4.8 years (SD 3.5). Those in specialist intellectual disability dementia care had a longer survival time (mean 9.5 years) than other settings (mean 3.4 to 4.1 years; p < 0.001). Late-onset myoclonic epilepsy in DS (LOMEDS) was linked to a threefold higher risk of death after onset (p < 0.001).

Discussion: Specialist care settings and LOMEDS timing significantly shape survival in DS-associated AD, highlighting the importance of tailored services and proactive epilepsy treatment.

Keywords: Alzheimer's disease; Down syndrome; Down syndrome‐associated Alzheimer's disease; LOMEDS; mortality; survival.

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Conflict of interest statement

JF reports receiving personal fees for service on the advisory boards, adjudication committees, or speaker honoraria from AC Immune, Adamed, Alzheon, Biogen, Eisai, Esteve, Fujirebio, Ionis, Laboratorios Carnot, Life Molecular Imaging, Lilly, Lundbeck, Perha, Roche, and Zambón, outside the submitted work. JF reports holding a patent for markers of synaptopathy in neurodegenerative disease (licensed to ADx, EPI8382175.0). MC‐I has received personal fees for service on advisory boards, speaker honoraria, or educational activities from IMSERSO, Esteve, Lilly, Neuraxpharm, Adium Pharma, and Roche. AL reported receiving personal fees for service on advisory boards of or speaker honoraria from Almirall, Beckman‐Coulter, Biogen, Eisai, Esteve, Fujirebio Europe, Grifols, KRKA, Lilly, Novartis, Novo Nordisk, Nutricia, Otsuka Pharmaceutical, Roche, and Zambón. AL is co‐author of a patent for markers of synaptopathy in neurodegenerative disease (licensed to ADx, EPI8382175.0) and on antibodies for amyloid precursor, methods, and uses thereof (European priority No. EP25382226). MA reported receiving speaker honoraria from Esteve Pharmaceuticals, Lilly, Neuraxpharm, Kern Pharma, Novo Nordisk, Zambon, and Nutricia. The other authors declared no potential conflicts of interest. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Flow chart for final study analytic sample. Flow chart showing how decedents from each cohort enter the analytic sample. Step 1 screens for an AD dementia diagnosis. Step 2 verifies AD as the fundamental cause of death. Solid arrows indicate inclusion; dotted arrows indicate exclusions such as non‐AD diagnoses, alternative causes of death, or missing cause‐of‐death data. Rounded boxes represent cohorts and the final analytic sample; rectangular boxes are decision nodes. Abbreviations: AD, Alzheimer's disease; ID, intellectual disability.
FIGURE 2
FIGURE 2
Age at diagnosis, age at death, and survival time distributions by Cohort. Left: kernel density curves for age at AD dementia diagnosis (teal) and age at death (pink); vertical solid lines mark cohort medians. The dotted line shows the average age of diagnosis and the average age at death from the meta‐analysis by Iulita et al. (2022). Right: Kaplan–Meier survival from AD dementia diagnosis to death with 95% confidence bands and numbers at risk.
FIGURE 3
FIGURE 3
Model‐based survival under hypothetical LOMEDS onset times. Predicted survival from age at AD symptom onset for hypothetical LOMEDS onset at 1.0, 2.9 (cohort median), and 5.0 years and for never developing LOMEDS, derived from the time‐dependent Cox model (hazard ratio [HR] LOMEDS present 3.37; HR per additional latency year 0.94). Vertical dotted lines mark model‐based median survival (4.9, 5.5, 6.8, and 8.1 years, respectively). The latency effect shows a non‐significant trend (p = 0.073). No proportional hazards violation (global Schoenfeld test p = 0.52). Colors: 1 year (blue), 2.9 years (green), 5 years (red), No LOMEDS (black). AD, Alzheimer's disease; LOMEDS, late‐onset myoclonic epilepsy in Down syndrome.
FIGURE 4
FIGURE 4
Kaplan–Meier survival curves by care setting at time of death. Time from first AD dementia diagnosis to death, stratified by care setting at death. Groups: ID and dementia specialist care (black), nursing home (blue), ID residential (green), community group home (red), at home with relative (gray). Abbreviations: AD, Alzheimer's disease; ID, intellectual disability.
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