Comparison of clinical and neuropathological diagnoses of neurodegenerative diseases in two centres from the Brains for Dementia Research (BDR) cohort

Abstract

Early detection and accurate diagnosis of neurodegenerative disorders may provide better epidemiological data, closer monitoring of disease progression and enable more specialised intervention. We analysed the clinical records and pathology of brain donations from 180 patients from two Brains for Dementia Research cohorts to determine the agreement between in-life clinical diagnosis and post-mortem pathological results. Clinical diagnosis was extracted from medical records and cases assigned into broad clinical groups; control, Alzheimer’s disease (AD), vascular dementia (CVD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) and combined diseases. Pathology was assessed blindly, and cases categorised into; control, intermediate AD, severe AD, CVD, AD and CVD combined, DLB, AD and DLB combined and frontotemporal lobar degeneration (FTLD), according to the major contributing pathologies. In more than a third of cases clinical diagnosis was different from final neuropathological diagnosis. The majority of AD, DLB and control clinical groups matched the pathological diagnosis; however, thirty-five percent of clinical AD cases showed additional prominent CVD or DLB pathology which had not been diagnosed clinically and twenty-five percent of clinical control cases were found to have intermediate Tau pathology (modified Braak stage III–IV) or CVD. CVD and AD + CVD clinical groups showed an average of only thirty-two percent pathological correlation, the majority actually having no CVD, and fifty-three percent of pathologically identified FTLD cases had been incorrectly clinically diagnosed. Our results underlie the importance of neuropathological confirmation of clinical diagnosis. The relatively low accuracy of clinical diagnosis demonstrates the need for standardised and validated diagnostic assessment procedures.

Visual hallucinations in Alzheimer's disease do not seem to be associated with chronic hypoperfusion of to visual processing areas V2 and V3 but may be associated with reduced cholinergic input to these areas

“…This was more likely for the AD with visual hallucinations and dementia with Lewy body groups. The rate of change of diagnosis was similar to other post-mortem series [40, 41].…”

Prognostic value of amyloid/tau/neurodegeneration (ATN) classification based on diagnostic cerebrospinal fluid samples for Alzheimer’s disease

“…An important point to emphasize is that these CSF biomarkers seem to have a prognostic value, independent of the final clinical diagnosis. In a recent study by Selvackadunco et al [ 24 ], clinical and post mortem histopathological diagnoses matched in only 115 out of 180 patients (64%). Despite recent advances in diagnostic biomarkers, misdiagnosis or incomplete diagnosis for patients with cognitive decline is still a frequent problem.…”

Blood-Based ATN Biomarkers of Alzheimer’s Disease: A Meta-Analysis

“…It relies on data gathered through clinical examination, patient and carer interview, with differential diagnosis guided by structural and/or glucose metabolism imaging [1]. The limitations of this approach have been highlighted by the demonstration that a significant proportion of patients diagnosed with AD have their diagnosis changed through in-vivo amyloid positron emission tomography [2] or post-mortem studies [3,4]. Syndrome-based AD definition is particularly problematic in the context of preclinical or prodromal disease which is where the major efforts of diseasemodification are currently focused [5].…”