brain atrophy

Overview

Brain atrophy refers to a reduction in brain volume caused by loss of neurons, glial cells, synapses, and/or the supporting neuropil, and it is typically assessed as a structural change on neuroimaging or in histopathology. It is not a single disease, but rather a biological process and imaging phenotype that can occur across many neurological and systemic conditions, including neurodegenerative disorders, cerebrovascular disease, multiple sclerosis, stroke, hypoxic-ischemic injury, and hematologic disorders.

Biologically, brain atrophy reflects cumulative tissue injury and remodeling. Depending on the underlying condition, it may arise from neuroaxonal loss, demyelination, inflammation, ischemia, blood–brain barrier dysfunction, gliosis, or impaired recovery after injury. Because it can track disease burden and progression, brain atrophy is widely used as an outcome measure in clinical and preclinical research, including studies of blood-based biomarkers, MRI-based neurodegeneration, and therapeutic interventions aimed at preserving brain volume.

Focus of Latest Publications

Recent studies have used brain atrophy as a longitudinal marker of neurodegeneration, disease progression, and treatment response across several disease contexts.

In cognitively unimpaired individuals, one study (PMID: 42224636) examined longitudinal associations between blood-based biomarkers and MRI-measured neurodegeneration, specifically asking how changes in circulating biomarkers relate to brain atrophy over time and what the temporal sequence of these processes may be. This places brain atrophy in the context of early, preclinical neurodegenerative change and biomarker dynamics.

In relapsing-remitting multiple sclerosis (RRMS), another study (PMID: 41638890) evaluated how brain atrophy rates vary with age. The authors noted that brain atrophy is increasingly used as an outcome measure in clinical trials in RRMS, but that the interaction between chronological age and MS-specific effects had not been well characterized. This indicates that atrophy is being treated not only as a marker of cumulative damage, but also as a potentially age-sensitive endpoint in therapeutic studies.

Brain atrophy was also used as a readout of injury severity and recovery in experimental models. In a mouse stroke study (PMID: 41999081), genetic deletion of MEGF10 in astrocytes reduced astrocyte proliferation and activation, glial scar formation, and extracellular matrix deposition, and this was followed by decreased brain atrophy and improved neurofunction recovery after stroke. This links atrophy to post-stroke tissue remodeling and suggests that limiting astrogliosis may help preserve brain structure. The study also referenced large ischemic stroke in the broader context of injury-related remodeling.

In a hypoxic-ischemic encephalopathy (HIE) mouse model (PMID: 41786046), consecutive treatment with β-hydroxybutyrate (BHB) improved motor function and reduced brain atrophy. This suggests that metabolic intervention can mitigate structural brain loss after hypoxic injury. The related entity 3-hydroxybutyrate is relevant here because BHB is a ketone body in that biochemical class.

In adults with sickle cell disease (PMID: 42133908), investigators tested whether successful hematopoietic stem cell transplant (HSCT) was associated with reduced brain atrophy or white matter hyperintensity (WMH) growth. This study frames atrophy as a potentially modifiable imaging outcome in a chronic systemic disease with cerebrovascular consequences.

Finally, in cerebral small vessel disease (CSVD) (PMID: 41962120), brain atrophy was listed among the characteristic imaging lesions used to identify disease burden, alongside WMH, lacunes, cerebral microbleeds, and enlarged perivascular spaces. The study assessed associations between accelerated biological aging and the presence and longitudinal progression of CSVD, reinforcing brain atrophy as part of the broader structural signature of small-vessel brain injury.

Across these studies, brain atrophy functions as a common endpoint linking biomarker research, aging, vascular injury, inflammatory remodeling, and treatment effects. It is therefore both a disease-associated phenotype and a quantitative measure of neuroprotection or neurodegeneration.

Key Publications

• Jun Longitudinal Change in Blood-Based Biomarkers and the Association With MRI-Measured Neurodegeneration in Cognitively Unimpaired Individuals. (Neurology, 2026, PMID 42224636): "We aimed to investigate longitudinal associations between blood-based biomarkers and brain atrophy, and the temporal sequence of these processes."
• Jun Brain atrophy rates vary with age in relapsing-remitting multiple sclerosis. (Journal of neurology, neurosurgery, and psychiatry, 2026, PMID 41638890): "Brain atrophy is increasingly used as an outcome measure in clinical trials in relapsing-remitting multiple sclerosis (RRMS), but little is known about how chronological age interacts with MS-specific effects."
• Jun Targeted Inhibition of MEGF10-Mediated Astrogliosis Reduces Glial Scar Formation and Promotes Neurofunction Recovery in Mice After Stroke. (Glia, 2026, PMID 41999081): "Genetic deletion of MEGF10 in astrocytes reduced astrocyte proliferation and activation, glial scar formation, and extracellular matrix deposition, subsequentially decreased brain atrophy and promoted neurofunction recovery of mice after stroke."
• May β-hydroxybutyrate alleviates motor impairment and neurological damage in hypoxic-ischemic encephalopathy mice. (Behavioural brain research, 2026, PMID 41786046): "Consecutive BHB treatment significantly improved motor function and reduced brain atrophy in HIE mice."
• May Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. (Neurology, 2026, PMID 42133908): "We tested whether successful HSCT for adults with SCD was associated with reduced brain atrophy or WMH growth."
• May Associations of Accelerated Biological Aging With the Presence and Longitudinal Progression of Cerebral Small Vessel Disease. (Neurology, 2026, PMID 41962120): "Cerebral small vessel disease (CSVD) is a major cause of dementia and stroke, typically identified by lesions such as white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy."