Post-infection brain atrophy accelerates cognitive and molecular changes underlying dementia

TL;DR

Infections may speed up brain shrinkage and cognitive decline linked to dementia, according to a study using brain scans and biomarkers.

Contribution

This study shows that post-infection brain atrophy is linked to faster cognitive decline and molecular changes in dementia.

Findings

Infections like respiratory and urinary tract infections are associated with accelerated parieto-temporal brain atrophy.

Infection history correlates with higher ADRD plasma biomarker levels and faster cognitive decline.

Greater post-infection brain atrophy is linked to more pronounced changes in verbal memory and NfL.

Abstract

Infections have been associated with a greater risk of Alzheimer’s disease and related dementias (ADRD), but it is unclear how infections influence structural brain patterns over time, and whether post-infection brain atrophy can accelerate cognitive decline and molecular changes underlying dementia.

Using the Baltimore Longitudinal Study of Aging (BLSA; n = 793; mean age = 70.1), we examined how infections relate to longitudinal changes in machine learning-derived, 3 T-MRI neuroimaging signatures, and leveraged the UK Biobank (UKB; 1,120; mean age = 62.9 yrs) to externally validate infection-brain atrophy relationships. Using the BLSA, we also asked if infection history and infection-related brain volume loss were associated with cognitive decline, amyloid-beta PET, and ADRD plasma biomarker trajectories (Aβ42/40, pTau-181, NfL, GFAP).

We detected accelerated parieto-temporal atrophy in BLSA participants with a history of upper respiratory tract, bacterial, and urinary tract infections (p < 0.05), as well as influenza and skin/subcutaneous infections (FDR p < 0.05). After demonstrating their associations with longitudinal neuroimaging signatures in the UKB and prevalent dementia in the BLSA, we found that infections were related to a greater burden of ADRD plasma biomarkers and accelerated rates of cognitive decline in BLSA participants. Integrating longitudinal brain scans, cognitive assessments, and plasma biomarker measurements, we identified infection-related changes in verbal memory and NfL that were more prominent among BLSA participants who experienced greater post-infection brain atrophy.

Along with demonstrating that infections mediate clinically relevant brain atrophy patterns, these findings highlight the consequences of post-infection brain volume loss on longitudinal neurocognitive outcomes and extend our understanding of the biological basis by which infections may contribute to neurodegeneration.

The online version contains supplementary material available at 10.1186/s13195-025-01924-2.

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