On gaps of clinical diagnosis of dementia subtypes: A study of Alzheimer's disease and Lewy body disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) and Lewy body disease (LBD) are most common dementias, and can occur concurrently (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation could be difficult. Yet it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectrums and demographic variables. We aimed to compare clinical diagnosis and post‐mortem autopsy‐confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.MethodParticipants were selected from the National Alzheimer’s Coordinating Center dataset, with autopsy‐confirmed AD and/or LBD results, and initial visits with Clinical Dementia Rating (CDR) of 0, 0.5, or 1.0. We analyzed the clinical AD and/or LBD diagnosis in first visits at each CDR stage. This analysis included precision (PPV), sensitivity and specificity of the clinical diagnosis, and disparities in these metrics by sex, race/ethnicity, age and education. If autopsy‐confirmed AD, LBD, or AD+LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.Result1887 qualified participants (Table 1) from September 1, 2005 to August 20, 2019 were included. Clinical AD+LBD diagnosis had poor sensitivity from 3% (CDR 0.5) to 6% (CDR 2.0). Over 60% of participants with autopsy‐confirmed AD+LBD were diagnosed clinically as AD (Table 2). Clinical AD diagnosis had low sensitivities at early dementia stage (57%) and low specificities at all stages (Table 3). Among participants clinically diagnosed as AD, over 33% had autopsy‐confirmed concurrent LBD neuropathology. Clinical LBD diagnosis had poor PPVs from mild cognitive impairment (22%) to severe dementia (20%). Within participants clinically diagnosed as LBD, 32% to 54% revealed autopsy‐confirmed AD+LBD pathology. When clinicians missed these three subtypes, “No cognitive impairment”, “Undecided” and “Primary progressive aphasia or behavioral variant frontotemporal dementia” were the leading alternative clinical diagnosis. With increasing dementia stages, the difference in clinical diagnosis accuracy significantly increased between White and Black/African‐American participants, and diagnosis quality significantly improved for males but not for females.ConclusionOur findings demonstrates that the clinical diagnosis of AD, LBD and AD+LBD are inaccurate and harbor significant disparities based on race and sex at all dementia stages.