Conventional MRI Could Help Assess the Integrity of Key Brain Connections Involved in Memory and Attention

• Researchers at CIEN demonstrate in a study funded by the Reina Sofía Foundation that a simple visual rating scale is associated with deterioration of the brain pathways involved in memory and attention.
• Published in Alzheimer’s & Dementia, the study validates an MRI visual rating scale through neuropathological analysis, using a unique model that allows brain images to be compared with subsequent analyses of donated brains.
• Damage to these pathways is greater in Alzheimer’s disease than in dementia with Lewy bodies and is exacerbated by vascular lesions and other age-related changes.

Conventional magnetic resonance imaging (MRI), of the kind routinely performed in hospitals, could help assess the integrity of the brain connections underlying memory and attention. This is the conclusion of a study conducted by the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIEN), part of the Carlos III Health Institute, funded by the Reina Sofía Foundation and published in Alzheimer’s & Dementia, the scientific journal of the Alzheimer’s Association.

The study, which adds to CIEN’s recent advances in research aimed at improving the diagnosis of Alzheimer’s disease and other dementias, is based on postmortem MRI scans performed on 55 donors from BT-CIEN, CIEN’s brain tissue bank. The study included cases of Alzheimer’s disease, dementia with Lewy bodies, mixed pathology involving both conditions, and other neurodegenerative diseases.

The images were acquired within hours of death and before autopsy, making it possible to directly compare the findings on MRI with those revealed by subsequent analysis of brain tissue.

A tool available to any hospital

Acetylcholine, a chemical messenger essential for memory and attention, is produced in a small region at the base of the brain and reaches the cortex through two major bundles of white matter fibres—the brain’s “wiring,” which connects different brain regions. Acetylcholine is also the target of drugs that have been used for decades to alleviate the symptoms of Alzheimer’s disease.

Until now, accurately assessing the condition of these pathways has required advanced MRI techniques used mainly in research. The study shows that a visual rating scale known as CHIPS (Cholinergic Pathways Hyperintensities Scale), which focuses on the regions traversed by these fibres, is associated with their microstructural damage. The scale shows a stronger association with damage to cholinergic pathways than conventional scales used to assess white matter lesions in the brain.

“We were able to demonstrate that the radiologist’s visual assessment of damage to the acetylcholine pathways on a conventional MRI scan provides a very useful indicator of the actual microstructural damage to these pathways,” explains Michel J. Grothe, head of CIEN’s Neuroimaging Platform and one of the study’s authors. “It is a tool already available to any radiology department, at a time when accurately identifying which brain systems are affected is more important than ever.”

The research stems from a collaboration between CIEN and Karolinska Institutet (Sweden), with contributions from the Czech Technical University in Prague, the University of Ljubljana (Slovenia), Amsterdam UMC (the Netherlands), and Fernando Pessoa Canarias University. Daniel Ferreira, from Karolinska Institutet, and Michel J. Grothe are the study’s senior authors, while Milan Nemy, from the Czech Technical University in Prague and Karolinska Institutet, and Francisco J. López-González are joint first authors.

Not just Alzheimer’s disease

The study compares brains from people with Alzheimer’s disease, dementia with Lewy bodies—the second most common cause of dementia—both conditions combined, and other neurodegenerative diseases. Damage is greater in Alzheimer’s disease and in cases with mixed pathology, but it is not determined solely by the primary disease. Among the neuropathological factors analysed, vascular lesions and hippocampal sclerosis were the factors most strongly associated with damage to these pathways.

“Being able to directly compare what we observe on MRI with the lesions subsequently identified through examination of the same brain gives us a unique opportunity to better understand the underlying causes of the changes we see in the images,” says Francisco J. López-González, a researcher at CIEN and first author of the study. “MRI provides us with an image of the brain, but neuropathological examination allows us to confirm what lies behind that image. Combining both perspectives in the same brains is an exceptional opportunity to advance our understanding of neurodegenerative diseases, and we owe it to the generosity of our donors and their families.”

A unique model worldwide

CIEN’s research is based at the Reina Sofía Foundation Alzheimer’s Centre, which serves both as a specialised care facility for people with dementia and as a scientific research centre. At the same site, people receive care throughout their lives, undergo clinical assessments and neuroimaging examinations, and, thanks to their donations, their brains are subsequently analysed. BT-CIEN receives donations from across the Community of Madrid and, with a total of 966 donations, constitutes the largest clinicopathological cohort in Spain.

“This work demonstrates the value of the model that CIEN and the Reina Sofía Foundation have been building together for almost two decades, bringing clinical care and follow-up, neuroimaging and neuropathology together at a single centre,” says Pascual Sánchez-Juan, Scientific Director of CIEN. “We have a distinctive capacity for research into neurodegenerative diseases, as we are one of the few centres that perform MRI scans after death, while the brain is still inside the skull and before it is removed. This allows us to link an individual’s clinical follow-up with images of their brain and subsequently with microscopic analysis of the tissue. Combining these approaches helps us understand the lesions underlying the signals observed on MRI and represents one of our centre’s greatest strengths.”

Article reference: López-González FJ, Nemy M, Jerele C, et al. Post mortem MRI of cholinergic white matter pathways across neurodegenerative diseases. Alzheimer's Dement. 2026; 22:e71851.