Experts in dementia predicted neuropathology using only clinical history and neuropsychological screening exams.
Across dementia subtypes, definitive diagnosis has historically been reserved for cases with neuropathological confirmation or positive genetic testing. These authors examined the accuracy of prospectively obtained clinical diagnoses compared with autopsy-based diagnoses for 228 patients evaluated at an early-onset dementia clinic (mean age at onset, 57 ±8 years).
Diagnoses were rendered using a standardized approach that used the following information: illness course; the relative prominence of cognitive, behavioral, and motor signs and symptoms; the specific pattern of cognitive deficits elicited by clinical history-taking and neuropsychological testing; and the degree of selectivity of the cognitive deficits. During the period of clinical examination of this cohort (1983–2008), the field of dementia study saw considerable clinical and molecular advances, and the authors adjusted the diagnostic algorithm to address these (e.g., diagnostic criteria for dementia with Lewy bodies, updated pathological criteria for frontotemporal lobar degeneration [FTLD]) to include the biomarker TDP-43). However, the authors report that no biomarkers, including neuroimaging, were used to make the clinical diagnoses.
The two most common clinical diagnoses in the series — Alzheimer disease (AD; 46% of cases) and FTLD (42% of cases) — had 97% sensitivity and specificity. The few cases diagnosed erroneously included two patients with clinical diagnoses of behavioral-variant frontotemporal dementia (bvFTD) found to have AD at autopsy and four patients with diagnoses of bvFTD who had corticobasal degeneration pathology.
Comment: The authors acknowledge the referral bias in this sample, reflected in the higher-than-expected percentage of FTLD cases and relative paucity of vascular pathology. This bias may in fact be a strength of the authors’ diagnostic algorithm: The referral bias harnesses expert clinical evaluation in a subspecialty dementia clinic to make accurate neuropathological predictions, with the ultimate goal of using disease-specific therapeutic interventions. Even as researchers develop and investigate increasingly novel (and expensive) biomarkers for neurodegenerative disease, focused clinical history and neurobehavioral examination can be remarkably accurate.
— Brandy R. Matthews, MD