# Putaminal hypermetabolism identifies Lewy body co‐pathology in Alzheimer's disease

## TL;DR

Putaminal hypermetabolism is a potential marker for Lewy body co-pathology in Alzheimer's disease, linked to cognitive decline.

## Contribution

Putaminal hypermetabolism is identified as a novel metabolic marker for Lewy body co-pathology in Alzheimer's disease.

## Key findings

- ADSAA+ cases showed putamen hypermetabolism and occipital hypometabolism compared to ADSAA−.
- Putamen hypermetabolism predicted faster cognitive decline and variability in both AD groups.
- Putaminal hypermetabolism improved cognitive decline prediction when added to AD models.

## Abstract

The clinical implications of brain hypermetabolism remain unexplored in Lewy body disease (LBD) co‐pathology in Alzheimer's disease (AD).

We investigated cognition, 18F‐fluorodeoxyglucose positron emission tomography (PET), and cerebrospinal fluid tau phosphorylated at threonine 181 (pTau181)/Aβ42 plus α‐synuclein seeding amplification assays (SAA) in controls, 217 SAA‐negative AD (ADSAA−), and 124 SAA‐positive AD (ADSAA+). Brain metabolism was assessed using subject residual profile (SRP) and standardized uptake value ratio (SUVR).

Compared to ADSAA−, ADSAA+ showed putamen SRP hypermetabolism and middle occipital gyrus (MOG) SUVR hypometabolism. SAA positivity correlated with putamen SRP hypermetabolism independently of pTau181/amyloid beta 42 (Aβ42). Its interaction with pTau181/Aβ42 influenced MOG SUVR, showing increased MOG SUVR with higher pTau181/Aβ42 in ADSAA+. Putamen SRP hypermetabolism predicted faster cognitive decline and greater variability in both groups. MOG SUVR hypometabolism correlated with them only in ADSAA−. Adding putamen SRP hypermetabolism to models, including SAA positivity and AD signature hypometabolism, improved the prediction of cognitive decline/variability, whereas MOG SUVR did not.

Putaminal hypermetabolism may serve as a robust metabolic marker of LBD co‐pathology in AD.

LB co‐pathology in AD alters regional brain metabolism.SRP analyses capture putaminal hypermetabolism for SAA positivity.SUVR analyses emphasize occipital hypometabolism for SAA positivity.Occipital metabolism correlates positively with AD severity in mixed AD‐LB.Putaminal, not occipital, metabolism predicts cognitive change over AD‐related metabolism and SAA.

LB co‐pathology in AD alters regional brain metabolism.

SRP analyses capture putaminal hypermetabolism for SAA positivity.

SUVR analyses emphasize occipital hypometabolism for SAA positivity.

Occipital metabolism correlates positively with AD severity in mixed AD‐LB.

Putaminal, not occipital, metabolism predicts cognitive change over AD‐related metabolism and SAA.