. 2025 Apr 11;17(1):19.

doi: 10.1186/s11689-025-09604-w.

Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome

Melissa R Jenkins¹, Jamie C Peven^{2

3}, Lauren Kubic^{2

4}, Benjamin L Handen², Sharon J Krinsky-McHale⁵, Christy L Hom⁶, Alice Lee², Dana L Tudorascu², Max McLachlan^{1

7}, Matthew Zammit^{1

7}, Davneet Minhas⁸, Weiquan Luo⁹, Charles Laymon^{8

9}, Joseph H Lee¹⁰, Ira Lott¹¹, Annie Cohen², Beau M Ances¹², H Diana Rosas¹³, Florence Lai¹³, Shahid H Zaman¹⁴, Elizabeth Head¹⁵, Mark Mapstone¹⁶, Bradley T Christian^{1

7

17}, Sigan L Hartley^{18

19}; Alzheimer Biomarker Consortium - Down syndrome

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
² Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
³ Behavioral Health Service Line, VA Pittsburgh Healthcare System, Pittsburgh, PA, 15240, USA.
⁴ University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵ Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 10314, USA.
⁶ Department of Psychiatry & Human Behavior, Irvine School of Medicine, University of California, Irvine, CA, 92697, USA.
⁷ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705, USA.
⁸ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15240, USA.
⁹ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15240, USA.
¹⁰ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Sergievsky Center, and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
¹¹ Department of Neurology, Irvine School of Medicine, University of California, Irvine, CA, 92617, USA.
¹² Department of Neurology, Washington University in St. Louis, St. Louis, MO, 63130, USA.
¹³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
¹⁴ Department of Psychiatry, University of Cambridge, Cambridge, UK.
¹⁵ Department of Pathology & Laboratory Medicine, Irvine School of Medicine, University of California, Irvine, CA, 92617, USA.
¹⁶ Department of Neurology, Irvine School of Medicine, University of California, Irvine, CA, 92697, USA.
¹⁷ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53705, USA.
¹⁸ Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA. slhartley@wisc.edu.
¹⁹ School of Human Ecology, University of Wisconsin-Madison, Madison, WI, 53705, USA. slhartley@wisc.edu.

PMID: 40217501
PMCID: PMC11987311
DOI: 10.1186/s11689-025-09604-w

Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome

Melissa R Jenkins et al. J Neurodev Disord. 2025.

. 2025 Apr 11;17(1):19.

doi: 10.1186/s11689-025-09604-w.

Authors

Affiliations

¹ Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
² Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
³ Behavioral Health Service Line, VA Pittsburgh Healthcare System, Pittsburgh, PA, 15240, USA.
⁴ University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵ Department of Psychology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, 10314, USA.
⁶ Department of Psychiatry & Human Behavior, Irvine School of Medicine, University of California, Irvine, CA, 92697, USA.
⁷ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, 53705, USA.
⁸ Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15240, USA.
⁹ Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15240, USA.
¹⁰ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Sergievsky Center, and Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
¹¹ Department of Neurology, Irvine School of Medicine, University of California, Irvine, CA, 92617, USA.
¹² Department of Neurology, Washington University in St. Louis, St. Louis, MO, 63130, USA.
¹³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
¹⁴ Department of Psychiatry, University of Cambridge, Cambridge, UK.
¹⁵ Department of Pathology & Laboratory Medicine, Irvine School of Medicine, University of California, Irvine, CA, 92617, USA.
¹⁶ Department of Neurology, Irvine School of Medicine, University of California, Irvine, CA, 92697, USA.
¹⁷ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, 53705, USA.
¹⁸ Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA. slhartley@wisc.edu.
¹⁹ School of Human Ecology, University of Wisconsin-Madison, Madison, WI, 53705, USA. slhartley@wisc.edu.

PMID: 40217501
PMCID: PMC11987311
DOI: 10.1186/s11689-025-09604-w

Abstract

Background: Adults with Down syndrome (DS) have a 90% lifetime risk for Alzheimer's disease (AD), with neurobiological pathology present decades prior to dementia onset. The profile and timing of cognitive decline in DS is well-documented. However, there is a small body of research on whether Behavioral and Psychological Symptoms of Dementia (BPSD) occur early on in the progression of AD in DS and are associated with early AD pathology (i.e., amyloid-beta [Aβ] and neurofibrillary tau tangles [NFT]).

Methods: Data were analyzed from 337 adults with DS (M = 45.13 years, SD = 9.53 years) enrolled in a large cohort study. The Reiss Screen for Maladaptive Behavior (RSMB) measured common behaviors reported in BPSD across up to four study cycles (spaced approximately 16 months apart). Linear mixed models estimated change in BPSD as predicted by baseline (a) dementia status (i.e., cognitively stable, mild cognitive impairment [MCI], or dementia), (b) Aβ positron emission tomography (PET) tracer [¹¹C] PiB, and (c) NFT PET tracer [¹⁸F]AV-1451. Models controlled for chronological age, sex, study site, premorbid intellectual disability level, APOE e4 allele carrier status, psychiatric diagnoses, and psychiatric medication use.

Results: Compared to cognitively stable participants, participants whose status was MCI or dementia, had significantly higher baseline RSMB subdomain scores. Increases in RSMB Depression-Behavioral, Depression-Physical, and Psychosis were observed for participants with MCI. Higher baseline Aβ and NFT were associated with higher RSMB Avoidant at baseline, and increases in RSMB Depression-Physical and Psychosis over time.

Conclusions: BPSD are an important part of AD in DS, particularly during the prodromal stage. Elevated Aβ and NFT predict higher initial avoidance and change in physical depression behaviors and may indicate MCI in adults with DS. Broader increases in BPSD are observed as adults with DS progress from early to late-stage dementia. Clinicians should rule out other possible causes of BPSD when screening for AD, such as stressful life experiences or co-occurring medical conditions. Caregivers of adults with DS should have resources on BPSD management and self-care strategies.

Keywords: Alzheimer’s disease; Amyloid; Down syndrome; Psychiatric symptoms; Tau.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: This multi-site study was approved by the Internal Review Boards of the University of Pittsburgh, University of Wisconsin Madison, and University of California, Irvine. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

**Fig. 1**
Marginal Means of RSMB Scores by Baseline Clinical AD Status. Note. Marginal means for the Reiss Screen of Maladaptive Behavior (RSMB) across four data collection cycles for depression-behavior (A) depression-physical (B), psychosis (C), and total (D) for cognitively stable (blue), mild cognitive impairment (green), and dementia (red)

**Fig. 2**
Marginal Means of RSMB Scores by Average Baseline Amyloid. Note. Marginal means for the Reiss Screen of Maladaptive Behavior (RSMB) across four data collection cycles for restricted and repetitive (A), depression-behavior (B), depression-physical (C), psychosis (D), paranoia (E), and total (F) for average or above average Aβ (green) and below average Aβ (blue)

**Fig. 3**
Marginal Means of RSMB Scores by Average Baseline Tau. Note. Marginal means for the Reiss Screen of Maladaptive Behavior (RSMB) across four data collection cycles for depression-physical (A), psychosis (B), and total (C) for average or above average neurofibrillary tau tangles (NFT) (green) and below average NFT (blue)

See this image and copyright information in PMC

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Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome

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Behavioral and psychological symptoms of dementia and Alzheimer's disease progression in Down syndrome

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