Factors affecting progression of non-Alzheimer dementia: a retrospective analysis with long-term follow-up

BACKGROUND: Non-Alzheimer’s dementias, including vascular dementia (VaD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD), possess unique characteristics and prognostic factors that remain poorly understood. This study aims to investigate the temporal course of these subtypes and identify the impact of functional, neuropsychiatric, and comorbid medical conditions on prognosis. Additionally, the relationship between hippocampal atrophy, white matter intensities, and disease progression will be examined, along with the identification of key covariates influencing slow or fast progression in non-Alzheimer’s dementias. METHODS: A total of 196 patients with non-Alzheimer’s dementias who underwent at least three comprehensive evaluations were included, with proportions of VaD, FTD, LBD, and PDD being 50, 19.39, 19.90, and 10.71%, respectively. Patient demographics, comorbidities, neuropsychiatric and neuroimaging parameters, and global evaluation were analyzed using appropriate statistical methods. The study followed patients for a mean duration of 62.57 ± 33.45 months (ranging from 11 to 198 months). RESULTS: The results from three different visits for each non-AD dementia case demonstrated significant differences in various measures across visits, including functional capacity (BDLAS), cognition (MMSE), and other neuropsychological tests. Notably, certain genotypes and hippocampal atrophy grades were more prevalent in specific subtypes. The results indicate that Fazekas grading and hippocampal atrophy were significant predictors of disease progression, while epilepsy, extrapyramidal symptoms, thyroid dysfunction, coronary artery disease, diabetes mellitus, hypertension, stroke, hyperlipidemia, sleep disorders, smoking, and family history of dementia were not significant predictors. BDLAS and EDLAS scores at the first and second visits showed significant associations with disease progression, while scores at the third visit did not. Group-based trajectory analysis revealed that non-AD cases separated into two reliable subgroups with slow/fast prognosis, showing high reliability (Entropy = 0.790, 51.8 vs. 48.2%). CONCLUSION: This study provides valuable insights into the temporal course and prognostic factors of non-Alzheimer’s dementias. The findings underscore the importance of considering functional, neuropsychological, and comorbid medical conditions in understanding disease progression. The significant associations between hippocampal atrophy, white matter intensities, and prognosis highlight potential avenues for further research and therapeutic interventions.