Cognitive Impairment in Neurodegenerative Diseases: A Trans-Diagnostic Approach Using a Lesion-Symptom Mapping Analysis

Abstract

Introduction Neurodegenerative disorders, such as Alzheimer’s disease (AD) and frontotemporal dementia (bvFTD), reflect a spectrum of cognitive impairments unified by cognitive decline. Traditional diagnostic approaches often overlook shared landscapes of these disorders. A transdiagnostic approach, cutting across conventional boundaries, may improve understanding of shared mechanisms. This study uses lesion-symptom mapping (LSM) to identify critical brain structures responsible for cognitive impairments.

Methods Patients diagnosed with Mild Cognitive Impairment (MCI), probable AD, and probable bvFTD were recruited from our memory clinic. Diagnoses were made by a multidisciplinary team using established criteria. Participants underwent detailed medical and neurological examinations, neuroimaging, cerebrospinal fluid analysis, and neuropsychological assessment. MRI scans were processed using FreeSurfer. LSM was used to assess correlations between brain structures and cognitive performance.

Results Significant correlations were found between neuropsychological test scores and atrophy in specific brain regions. The Free and Cued Selective Reminding Test was linked to the right hippocampus and left nucleus accumbens. The Brief Visuospatial Memory Test-Revised correlated with the right hippocampus, left nucleus accumbens, and right middle temporal gyrus. Verbal fluency was linked to the left superior temporal sulcus and left middle temporal gyrus. Digit Span forward correlated with left superior frontal gyrus and left inferior parietal region, while Digit Span backward was linked to the right precuneus. Digit-Symbol Coding was associated with the left inferior parietal region.

Conclusions This study highlights common neural targets in MCI, AD, and bvFTD and their link with cognitive impairment, emphasizing the value of LSM within a transdiagnostic approach to neurodegenerative diseases.

Note:
Funding declaration: No funding was received for conducting this study.

Conflict of Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical Approval: This study was approved by the Ethics Review Board of the Faculty of Medicine of the University of Coimbra (FMUC), with reference number CE-032/2021.

Keywords: cognition, Alzheimer's Disease, frontotemporal dementia, Mild Cognitive Impairment, Lesion-symptom mapping