Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome

doi:10.1002/alz.70387

Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome

Research output: Contribution to journal › Article › peer-review

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Abstract

INTRODUCTION: Weight loss has been linked to early Alzheimer's disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline. METHODS: Adults with DS (N = 467; M_age= 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms. RESULTS: BMI declined with age-by-time (β = −0.014, p = 0.002) and baseline PET Aβ-by-time (β = −0.005, p = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning. DISCUSSION: Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms. Highlights: Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer's disease (DSAD). On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s. Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS. Across time, AD-related memory declines are associated with BMI decline. BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.

Original language	English
Article number	e70387
Journal	Alzheimer's and Dementia
Volume	21
Issue number	6
DOIs	https://doi.org/10.1002/alz.70387
State	Published - Jun 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

Data collection and sharing for this project was supported by The Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) funded by the National Institute on Aging (NIA) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 AG051406 and U01 AG051412). All research at the Department of Psychiatry at the University of Cambridge is supported by the National Institure for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (NIHR203312) and the NIHR Applied Research Collaboration East of England. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The authors thank the adults with Down syndrome who volunteered to participate in this study for their invaluable contributions to this work, along with their families and service providers. Finally, the authors thank the staff contributing the many hours of support to the collection of data, including Jessica Beresford-Webb, Malwina Filipczuk, Shemaya Hurd-Thomas, Shara Khoo, and Ellie Maycock. This research was funded by the NIA (F31AG085730; K01AG083130; R01AG070028; U01AG051412; U19AG068054). This study was supported in part by a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P50HD105353). This study was also supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312) and the NIHR Applied Research Collaboration East of England.

Funders	Funder number
Alberta Blue Cross
National Institute for Health and Care Research
National Institute on Aging
NIHR Cambridge Biomedical Research Centre	F31AG085730, NIHR203312, R01AG070028, U01AG051412, U19AG068054, K01AG083130
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research	P50HD105353
Eunice Kennedy Shriver National Institute of Child Health and Human Development	U01 AG051412, U01 AG051406

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ABC-DS
Alzheimer's disease
Down syndrome
amyloid beta
cognition
trisomy 21
weight loss

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Access to Document

10.1002/alz.70387

Cite this

@article{e36faf6147e746d596defa7c60433cc4,

title = "Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome",

abstract = "INTRODUCTION: Weight loss has been linked to early Alzheimer's disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline. METHODS: Adults with DS (N = 467; Mage= 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms. RESULTS: BMI declined with age-by-time (β = −0.014, p = 0.002) and baseline PET Aβ-by-time (β = −0.005, p = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning. DISCUSSION: Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms. Highlights: Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer's disease (DSAD). On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s. Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS. Across time, AD-related memory declines are associated with BMI decline. BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.",

keywords = "ABC-DS, Alzheimer's disease, Down syndrome, amyloid beta, cognition, trisomy 21, weight loss",

author = "Fleming, \{Victoria L.\} and Helsel, \{Brian C.\} and Ptomey, \{Lauren T.\} and Handen, \{Benjamin L.\} and Krinsky-McHale, \{Sharon J.\} and Hom, \{Christy L.\} and Matthew Zammit and Davneet Minhas and Weiquan Luo and Charles Laymon and Lee, \{Joseph H.\} and Ira Lott and Annie Cohen and Ances, \{Beau M.\} and Brickman, \{Adam M.\} and Margaret Pulsifer and Clare, \{Isabel C.H.\} and Rosa, \{H. Diana\} and Florencia Lai and Jordan Harp and Fredrick Schmitt and Julie Price and Zaman, \{Shahid H.\} and Elizabeth Head and Mark Mapstone and Christian, \{Bradley T.\} and Ozioma Okonkwo and Hartley, \{Sigan L.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2025",

month = jun,

doi = "10.1002/alz.70387",

language = "English",

volume = "21",

number = "6",

}

TY - JOUR

T1 - Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome

AU - Fleming, Victoria L.

AU - Helsel, Brian C.

AU - Ptomey, Lauren T.

AU - Handen, Benjamin L.

AU - Krinsky-McHale, Sharon J.

AU - Hom, Christy L.

AU - Zammit, Matthew

AU - Minhas, Davneet

AU - Luo, Weiquan

AU - Laymon, Charles

AU - Lee, Joseph H.

AU - Lott, Ira

AU - Cohen, Annie

AU - Ances, Beau M.

AU - Brickman, Adam M.

AU - Pulsifer, Margaret

AU - Clare, Isabel C.H.

AU - Rosa, H. Diana

AU - Lai, Florencia

AU - Harp, Jordan

AU - Schmitt, Fredrick

AU - Price, Julie

AU - Zaman, Shahid H.

AU - Head, Elizabeth

AU - Mapstone, Mark

AU - Christian, Bradley T.

AU - Okonkwo, Ozioma

AU - Hartley, Sigan L.

PY - 2025/6

Y1 - 2025/6

N2 - INTRODUCTION: Weight loss has been linked to early Alzheimer's disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline. METHODS: Adults with DS (N = 467; Mage= 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms. RESULTS: BMI declined with age-by-time (β = −0.014, p = 0.002) and baseline PET Aβ-by-time (β = −0.005, p = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning. DISCUSSION: Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms. Highlights: Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer's disease (DSAD). On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s. Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS. Across time, AD-related memory declines are associated with BMI decline. BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.

AB - INTRODUCTION: Weight loss has been linked to early Alzheimer's disease (AD) pathology, possibly through metabolic dysregulation. We examined changes in body mass index (BMI) in relation to AD biomarkers (amyloid beta [Aβ] and tau) and cognitive decline in adults with Down syndrome (DS). We hypothesized that BMI decline would track with early AD pathology and cognitive decline. METHODS: Adults with DS (N = 467; Mage= 43.67 ± 10.06) completed one to four data cycles (≈16 months apart). Linear mixed models examined BMI change over time by age, positron emission tomography (PET) Aβ and tau, and changes in memory and dementia symptoms. RESULTS: BMI declined with age-by-time (β = −0.014, p = 0.002) and baseline PET Aβ-by-time (β = −0.005, p = 0.002). On average, BMI decline began in the early 40s and was related to decline in memory and overall cognitive functioning. DISCUSSION: Weight loss is associated with the presence of Aβ and cognitive decline in adults with DS. Longitudinal studies need to clarify directionality and biological mechanisms. Highlights: Adults with Down syndrome (DS) are at an elevated risk for Down Syndrome assocaited Alzheimer's disease (DSAD). On average, adults with DS experience body mass index (BMI) decline beginning in their early 40s. Positron emission tomography amyloid beta deposition is associated with greater decline in BMI in adults with DS. Across time, AD-related memory declines are associated with BMI decline. BMI decline should be part of DSAD screening tools, as it is an important part of DSAD clinical disease expression.

KW - ABC-DS

KW - Alzheimer's disease

KW - Down syndrome

KW - amyloid beta

KW - cognition

KW - trisomy 21

KW - weight loss

UR - https://www.scopus.com/pages/publications/105009639233

UR - https://www.scopus.com/pages/publications/105009639233#tab=citedBy

U2 - 10.1002/alz.70387

DO - 10.1002/alz.70387

M3 - Article

C2 - 40545561

AN - SCOPUS:105009639233

SN - 1552-5260

VL - 21

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

M1 - e70387

ER -

Longitudinal study of body mass index in relation to Alzheimer's disease pathology and symptomatology in Down syndrome

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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