Impact of the polygenic risk scores for attention-deficit/hyperactivity disorder in Alzheimer's disease

IF 13 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-25 DOI:10.1002/alz.70003

Douglas T. Leffa, Guilherme Povala, Bruna Bellaver, João Pedro Ferrari-Souza, Pamela C. L. Ferreira, Firoza Z. Lussier, Cristiano Schaffer Aguzzoli, Carolina Soares, Hussein Zalzale, Francieli Rohden, Guilherme Bauer-Negrini, Sarah Abbas, Maitê Schneider, Joseph Therriault, Oscar L. Lopez, Victor L. Villemagne, William E. Klunk, Dana L. Tudorascu, Ann D. Cohen, Pedro Rosa-Neto, Eduardo R. Zimmer, Thomas K. Karikari, Luis Augusto Rohde, Brooke S. G. Molina, Tharick A. Pascoal, the Alzheimer's Disease Neuroimaging Initiative

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引用次数: 0

Abstract

INTRODUCTION

Epidemiological studies indicate a link between attention-deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear.

METHODS

We computed weighted ADHD polygenic risk scores (ADHD-PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.5 years). A subset underwent cerebrospinal fluid (CSF) analysis for amyloid beta (Aβ) and phosphorylated tau, as well as fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET).

RESULTS

We observed lower executive function in individuals with high ADHD-PRS for both MCI and dementia participants. Higher levels of CSF phosphorylated tau, but not Aβ, were observed in dementia participants with higher ADHD-PRS. Increased ADHD-PRS was associated with glucose hypometabolism in the frontal and parietal cortices.

DISCUSSION

ADHD-PRS is associated with a more severe disease presentation in individuals with cognitive impairment due to dementia, characterized by impaired executive function, elevated tau pathology, and hypometabolism in the frontal and parietal cortices.

Highlights

We calculated the genetic liability for attention-deficit/hyperactivity disorder (ADHD) using polygenic risk scores (ADHD-PRS).
Elevated ADHD-PRS was associated with executive function deficits in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia.
Higher levels of cerebrospinal fluid (CSF) phosphorylated tau, but not amyloid beta (Aβ), were observed in dementia participants with higher ADHD-PRS.
Higher ADHD-PRS was associated with brain hypometabolism in individuals with AD dementia.
Hypometabolism in the parietal cortex mediated the effects of ADHD-PRS on executive function.

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.