Clinical, Radiological, and Immunohistological Distinctions Between Limbic-Predominant and Typical Alzheimer's...

Alzheimer's disease (AD) is the most common cause of dementia worldwide and one of the leading causes of morbidity and mortality among elderly people. It is characterized by generalized brain atrophy, especially affecting the hippocampus and medial temporal lobe. In this context, new subtypes of AD have been documented, including a limbic-predominant subtype (LP), and the current literature is insufficient to clarify the similarities and differences between these subtypes and the typical presentation. Recently, new studies have proposed a clinical criterion for LP amnestic syndrome, separating it from AD. Therefore, this study aims to evaluate the clinical, radiological, and immunohistological distinctions between those two presentations.

This study was conducted in accordance with the PRISMA guidelines. Notable databases were utilized for sources: PubMed, Embase, and Web of Science. Baseline characteristics, clinical, radiological, and immunohistological features, and follow-up times were recorded. Screening was performed using the Rayyan system, and quality assessment was conducted using appropriate tools.

After reviewing 211 articles, screening yielded 21 articles, totaling 11,315 patients. Among these, 1178 (15.7%) presented with LP and 4159 (36.7%) with AD. A total of 5378 (47.6%) had a different presentation, including hippocampal sparing only and the association of LP and typical AD. The weighted average for education in years was 24.31 for LP patients and 17.15 for typical AD patients. The weighted average for age at onset was 72.33 for typical AD patients and 77.36 for LP patients. For the duration of the disease, the weighted average for typical AD was 8.95, and it was 8.43 for LP. There were no differences in clinical presentation, with cognitive impairment and memory deficits being the most cited manifestations. MRI and FDG-PET are the most commonly used imaging techniques; in typical AD patients, different levels of hippocampal and medial, lateral parietal, and frontotemporal lobe atrophy are observed. In LP patients, imaging findings revealed lower hippocampal volume and higher metabolic rates than in typical AD patients. MRI R2 relaxometry in LP patients revealed lower R2 relaxation rates in the amygdala, hippocampus, and temporal lobe white matter compared with typical AD patients. Tau-PET imaging in typical AD patients demonstrated elevated standardized uptake value ratios in the parietal and posterior cingulate cortex. The immunohistological findings revealed a greater hippocampal tau burden than in cortical regions and a greater number of TDP-43 inclusions in LP patients than in typical AD patients. Typical AD patients had a weighted average of 20.06 and LP patients 17.7.

Our analysis of clinical, radiological, and immunohistological features revealed significant differences between LP and typical AD presentations. However, those findings alone cannot reliably determine accuracy, whether both presentations are stages of the same pathology or different diseases. More studies need to explore this field to further examine this topic.