Clinical characteristics of patients with suspected Alzheimer’s disease within a CSF Aß-ratio grey zone

BACKGROUND: The AT(N) research framework for Alzheimer's disease (AD) remains unclear on how to best deal with borderline cases. Our aim was to characterise patients with suspected AD with a borderline Aß(1-42)/Aß(1-40) ratio in cerebrospinal fluid. METHODS: We analysed retrospective data from two cohorts (memory clinic cohort and ADNI) of patients (n = 63) with an Aß(1-42)/Aß(1-40) ratio within a predefined borderline area—Q(1) above the validated cut-off value(grey zone). We compared demographic, clinical, neuropsychological and neuroimaging features between grey zone patients and patients with low Aß(1-42) (normal Aß ratio but pathological Aß(1-42), n = 42) and patients with AD (pathological Aß, P-Tau, und T-Tau, n = 80). RESULTS: Patients had mild cognitive impairment or mild dementia and a median age of 72 years. Demographic and general clinical characteristics did not differ between the groups. Patients in the grey zone group were the least impaired in cognition. However, they overlapped with the low Aß(1-42) group in verbal episodic memory performance, especially in delayed recall and recognition. The grey zone group had less severe medial temporal atrophy, but mild posterior atrophy and mild white matter hyperintensities, similar to the low Aß(1-42) group. CONCLUSIONS: Patients in the Aß ratio grey zone were less impaired, but showed clinical overlap with patients on the AD continuum. These borderline patients may be at an earlier disease stage. Assuming an increased risk of AD and progressive cognitive decline, careful consideration of clinical follow-up is recommended when using dichotomous approaches to classify Aß status. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42466-023-00262-8.