Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy

Michelle M Mielke; Sarah A Gaussoin; Ramon Casanova; Lauren A Latham; JoAnn E Manson; Charles P Mouton; Ted K S Ng; Stephen R Rapp; Susan M Resnick; Bonnie C Sachs; Nazmus Saquib; Aladdin H Shadyab; Linda K McEvoy; Andrea Z LaCroix; Robert B Wallace; Mark A Espeland; Jiu-Chiuan Chen; Kathleen M Hayden

doi:10.1002/alz.71704

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Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy

Journal article

Open access

Peer reviewed

Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy

Michelle M Mielke, Sarah A Gaussoin, Ramon Casanova, Lauren A Latham, JoAnn E Manson, Charles P Mouton, Ted K S Ng, Stephen R Rapp, Susan M Resnick, Bonnie C Sachs, …

Alzheimer's & dementia, Vol.22(7), e71704

07/2026

DOI: 10.1002/alz.71704

PMID: 42509652

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Abstract

Cognitive impairment among older adults is often due to multiple pathologies and heterogenous risk factors. We assessed whether Alzheimer's blood-based biomarkers (BBMs) were associated with incident mild cognitive impairment (MCI)/probable dementia, and whether associations were modified by age, apolipoprotein E (APOE), and hormone therapy (HT). Analyses included 2467 Women's Health Initiative Memory Study women (≥65 years of age) randomized between 1995 and 1998 to 3-5-years of HT or placebo. Cox regression (mean 18-year follow-up) assessed associations between the z-scored BBMs and MCI/dementia. Lower baseline amyloid beta (Aβ)42/40 ratio and higher phosphorylated tau 181 (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were associated with an increased risk of MCI and dementia; GFAP was most strongly associated. The p-tau181 and NfL associations were stronger among APOE ε4 carriers; BBMs varied non-linearly by age. The associations of BBMs with the cognitive outcomes also varied inconsistently between HT groups. BBMs for AD and related dementias (ADRD) are associated with incident MCI/dementia in older women. Interactions between the BBMs and HT were inconsistent and require further investigation.

Age Factors

Aged

Aged, 80 and over

Alzheimer Disease - blood

Amyloid beta-Peptides - blood

Apolipoproteins E - genetics

Biomarkers - blood

Cognitive Dysfunction - blood

Cognitive Dysfunction - epidemiology

Cognitive Dysfunction - genetics

Dementia - blood

Dementia - epidemiology

Dementia - genetics

Female

Glial Fibrillary Acidic Protein - blood

Humans

Incidence

Neurofilament Proteins - blood

Peptide Fragments - blood

tau Proteins - blood

Details

Title: Subtitle: Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy
Creators: Michelle M Mielke - Wake Forest University
Sarah A Gaussoin - Wake Forest University
Ramon Casanova - Wake Forest University
Lauren A Latham - Wake Forest University
JoAnn E Manson - Brigham and Women's Hospital
Charles P Mouton - The University of Texas Medical Branch at Galveston
Ted K S Ng - Rush University Medical Center
Stephen R Rapp - Wake Forest University
Susan M Resnick - University of Pennsylvania
Bonnie C Sachs - Wake Forest University
Nazmus Saquib - Sulaiman Al Rajhi Colleges
Aladdin H Shadyab - University of California San Diego
Linda K McEvoy - Kaiser Permanente Washington Health Research Institute
Andrea Z LaCroix - Human Longevity (United States)
Robert B Wallace - University of Iowa
Mark A Espeland - Wake Forest University
Jiu-Chiuan Chen - University of Southern California
Kathleen M Hayden - Wake Forest University
Resource Type: Journal article
Publication Details: Alzheimer's & dementia, Vol.22(7), e71704
DOI: 10.1002/alz.71704
PMID: 42509652
NLM abbreviation: Alzheimers Dement
ISSN: 1552-5260
eISSN: 1552-5279
Publisher: Wiley
Grant note: NIA NIH HHS 75N92021D00002 / NHLBI NIH HHS NHLBI NIH HHS NIH HHS 75N92021D00003 / WHI NIH HHS 75N92021D00001 / NHLBI NIH HHS 75N92021D00005 / WHI NIH HHS 75N92021D00004 / WHI NIH HHS
Language: English
Date published: 07/2026
Academic Unit: Epidemiology; Injury Prevention Research Center
Record Identifier: 9985215016202771

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