Frontotemporal dementia and dementia with Lewy bodies in a case-control study of Alzheimer's disease

Background: The clinical presentations in dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) overlap considerably with that of Alzheimer's disease (AD) despite different pathological processes. Autopsy studies have also shown that multiple brain pathology occurs frequently, even in cases with a single clinical diagnosis. We aimed to determine the frequency of clinical diagnosis of FTD and DLB and the underlying pathology in a well-characterized cohort of patients with a clinical diagnosis of probable or possible AD. Methods: We conducted a retrospective analysis of 170 AD patients (probable AD = 83; possible AD = 87) originally enrolled in a case-control study, 27 with postmortem examination, to establish the number of cases meeting probable diagnosis for FTD and DLB, using a checklist of features compiled from their consensus criteria. Results: 23/83 probable AD cases and 32/87 possible AD cases met probable criteria for another dementia, more commonly DLB than FTD. AD pathology was present in 8/15 probable AD and 8/12 possible AD cases coming to autopsy. DLB pathology was seen in four cases and FTD pathology in eight cases. In the AD cases reaching clinical diagnosis for a second dementia syndrome and coming to autopsy, a minority showed non-AD pathology only. Conclusions: Presence of core clinical features of non-AD dementia syndromes is common in AD. Concordance between clinical and pathological diagnoses of dementia remains variable. We propose that repeat clinical examinations and structural neuroimaging will improve diagnostic accuracy. In addition, clinical diagnostic criteria for the main dementia syndromes require refinement.