Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease

Nadia Ramsingh; Hung Mo Lin; Yuxia Ouyang; Ramit Ravona-Springer; Abigail Livny; Laili Soleimani; Barbara B. Bendlin; Adar Matatov; Tal Niv; Tamar Shamir; Ithamar Ganmore; Anthony Heymann; Mary Sano; Joseph Azuri; Michal Schnaider Beeri

doi:10.1002/gps.70060

Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease

Nadia Ramsingh^*
, Hung Mo Lin
, Yuxia Ouyang
, Ramit Ravona-Springer
, Abigail Livny
, Laili Soleimani
, Barbara B. Bendlin
, Adar Matatov
, Tal Niv
, Tamar Shamir
, Ithamar Ganmore
, Anthony Heymann
, Mary Sano
, Joseph Azuri
, Michal Schnaider Beeri

^*Corresponding author for this work

Department of Psychiatry
Icahn School of Medicine at Mount Sinai
Yale University
Department of Genetics and Genomic Science
Sheba Medical Center at Tel Hashomer
Department of Medicine
University of Wisconsin-Madison
Faculty of Medicine
Tel Aviv University
Memory Clinic and Department of Neurology
Maccabi Healthcare Services
Meuhedat Healthcare
VA Medical Center
Krieger Klein Alzheimer's Research Center
Rutgers - The State University of New Jersey, New Brunswick

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

1 Scopus citations

Abstract

Objective: To assess the relationship of subtle preclinical cognitive changes with white matter microstructure and cortical volume in middle-aged adults at high AD risk due to a parental history. Methods: Participants (n = 278) were AD patients' offspring from the Israel Registry for Alzheimer's Prevention study. Cognitively unimpaired-decliners (CU-D) were based on a linear regression model. In a subsample with MRI (n = 220), we examined relationships of CU-D with white matter (WM) microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) and cortical volume in brain regions commonly affected in AD. Results: CU-D participants had lower FA in the superior longitudinal fasciculus (SLF) (p = < 0.001) and higher MD in the SLF (p = < 0.001), and cingulum adjacent to the corpus callosum (p = < 0.001) and genu (p = 0.006) compared to cognitively unimpaired-stable (CU-S) participants. The groups did not differ in cortical brain volumes. Conclusions: CU-D participants had poorer WM microstructure in brain tracts affected early in AD. Early interventions can target individuals that fit the CU-D criteria.

Original language	English
Article number	e70060
Journal	International Journal of Geriatric Psychiatry
Volume	40
Issue number	3
DOIs	https://doi.org/10.1002/gps.70060
State	Published - Mar 2025

Funding

Funders	Funder number
LeRoy Schecter Foundation
National Institutes of Health	R01AG043878, R21AG080827, P30AG066514
Alzheimer's Association	AACSF-21-852173, AACSF-21-851587

Keywords

Alzheimer's disease
cognitive-unimpaired declining
cortical volume
family history
white matter microstructure

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10.1002/gps.70060

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Ramsingh, N., Lin, H. M., Ouyang, Y., Ravona-Springer, R., Livny, A., Soleimani, L., Bendlin, B. B., Matatov, A., Niv, T., Shamir, T., Ganmore, I., Heymann, A., Sano, M., Azuri, J., & Beeri, M. S. (2025). Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease. International Journal of Geriatric Psychiatry, 40(3), Article e70060. https://doi.org/10.1002/gps.70060

@article{dc1f472575dd45adbe3e0a0a785e28e2,

title = "Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease",

abstract = "Objective: To assess the relationship of subtle preclinical cognitive changes with white matter microstructure and cortical volume in middle-aged adults at high AD risk due to a parental history. Methods: Participants (n = 278) were AD patients' offspring from the Israel Registry for Alzheimer's Prevention study. Cognitively unimpaired-decliners (CU-D) were based on a linear regression model. In a subsample with MRI (n = 220), we examined relationships of CU-D with white matter (WM) microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) and cortical volume in brain regions commonly affected in AD. Results: CU-D participants had lower FA in the superior longitudinal fasciculus (SLF) (p = < 0.001) and higher MD in the SLF (p = < 0.001), and cingulum adjacent to the corpus callosum (p = < 0.001) and genu (p = 0.006) compared to cognitively unimpaired-stable (CU-S) participants. The groups did not differ in cortical brain volumes. Conclusions: CU-D participants had poorer WM microstructure in brain tracts affected early in AD. Early interventions can target individuals that fit the CU-D criteria.",

keywords = "Alzheimer's disease, cognitive-unimpaired declining, cortical volume, family history, white matter microstructure",

author = "Nadia Ramsingh and Lin, \{Hung Mo\} and Yuxia Ouyang and Ramit Ravona-Springer and Abigail Livny and Laili Soleimani and Bendlin, \{Barbara B.\} and Adar Matatov and Tal Niv and Tamar Shamir and Ithamar Ganmore and Anthony Heymann and Mary Sano and Joseph Azuri and Beeri, \{Michal Schnaider\}",

note = "Publisher Copyright: {\textcopyright} 2025 John Wiley \& Sons Ltd.",

year = "2025",

month = mar,

doi = "10.1002/gps.70060",

language = "אנגלית",

volume = "40",

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issn = "0885-6230",

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Ramsingh, N, Lin, HM, Ouyang, Y, Ravona-Springer, R , Livny, A, Soleimani, L, Bendlin, BB, Matatov, A, Niv, T, Shamir, T, Ganmore, I, Heymann, A, Sano, M, Azuri, J & Beeri, MS 2025, 'Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease', International Journal of Geriatric Psychiatry, vol. 40, no. 3, e70060. https://doi.org/10.1002/gps.70060

TY - JOUR

T1 - Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease

AU - Ramsingh, Nadia

AU - Lin, Hung Mo

AU - Ouyang, Yuxia

AU - Ravona-Springer, Ramit

AU - Livny, Abigail

AU - Soleimani, Laili

AU - Bendlin, Barbara B.

AU - Matatov, Adar

AU - Niv, Tal

AU - Shamir, Tamar

AU - Ganmore, Ithamar

AU - Heymann, Anthony

AU - Sano, Mary

AU - Azuri, Joseph

AU - Beeri, Michal Schnaider

PY - 2025/3

Y1 - 2025/3

N2 - Objective: To assess the relationship of subtle preclinical cognitive changes with white matter microstructure and cortical volume in middle-aged adults at high AD risk due to a parental history. Methods: Participants (n = 278) were AD patients' offspring from the Israel Registry for Alzheimer's Prevention study. Cognitively unimpaired-decliners (CU-D) were based on a linear regression model. In a subsample with MRI (n = 220), we examined relationships of CU-D with white matter (WM) microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) and cortical volume in brain regions commonly affected in AD. Results: CU-D participants had lower FA in the superior longitudinal fasciculus (SLF) (p = < 0.001) and higher MD in the SLF (p = < 0.001), and cingulum adjacent to the corpus callosum (p = < 0.001) and genu (p = 0.006) compared to cognitively unimpaired-stable (CU-S) participants. The groups did not differ in cortical brain volumes. Conclusions: CU-D participants had poorer WM microstructure in brain tracts affected early in AD. Early interventions can target individuals that fit the CU-D criteria.

AB - Objective: To assess the relationship of subtle preclinical cognitive changes with white matter microstructure and cortical volume in middle-aged adults at high AD risk due to a parental history. Methods: Participants (n = 278) were AD patients' offspring from the Israel Registry for Alzheimer's Prevention study. Cognitively unimpaired-decliners (CU-D) were based on a linear regression model. In a subsample with MRI (n = 220), we examined relationships of CU-D with white matter (WM) microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) and cortical volume in brain regions commonly affected in AD. Results: CU-D participants had lower FA in the superior longitudinal fasciculus (SLF) (p = < 0.001) and higher MD in the SLF (p = < 0.001), and cingulum adjacent to the corpus callosum (p = < 0.001) and genu (p = 0.006) compared to cognitively unimpaired-stable (CU-S) participants. The groups did not differ in cortical brain volumes. Conclusions: CU-D participants had poorer WM microstructure in brain tracts affected early in AD. Early interventions can target individuals that fit the CU-D criteria.

KW - Alzheimer's disease

KW - cognitive-unimpaired declining

KW - cortical volume

KW - family history

KW - white matter microstructure

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U2 - 10.1002/gps.70060

DO - 10.1002/gps.70060

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C2 - 40050014

AN - SCOPUS:86000683988

SN - 0885-6230

VL - 40

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 3

M1 - e70060

ER -

Brain Signatures of Very Early Cognitive Decline in Asymptomatic Middle-Aged Offspring of People With Alzheimer's Disease

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Keywords

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