Episodic memory impairment and brain amyloid-beta (Aβ) are two of the main hallmarks of Alzheimer’s Disease (AD). In patients with suspected AD, these are often evaluated through neuropsychological testing and amyloid PET imaging (API), respectively. Crucially, the use of amyloid PET in clinical practice is only indicated in patients with substantial diagnostic uncertainty due to atypical clinical presentation, multiple comorbidities and/or early age of onset. The relationship between Aβ and cognition has been previously investigated, but no study has examined how neuropsychological features relate to the presence of amyloid pathology in the clinical population meeting the appropriate use criteria for API.
In this study, we evaluated a clinical cohort of patients (n=107) who presented at the Imperial Memory Clinic and were referred for clinical API and neuropsychological assessment as part of their diagnostic workup. We compared the cognitive performance of amyloid-positive patients (Aβ-pos, n=47) with that of stable amyloid-negative (stableAβ-neg, n=26) and progressive amyloid-negative (progAβ-neg, n=34) patients.
The Aβ-pos group performed significantly worse than both the amyloid- negative groups in the visuospatial and working memory domains. Episodic memory performance, instead, effectively differentiated the Aβ-pos group from the stableAβ-neg but not the progAβ-neg group. On affective questionnaires, the stableAβ-neg group reported significantly higher levels of depression than the Aβ-pos group.
In our clinical cohort, visuospatial dysfunction and working memory impairment were better indicators of amyloid positivity than episodic memory dysfunction. These findings highlight the limited value of isolated cognitive scores in patients with atypical clinical presentation, comorbidities and/or early age of onset.