Mild cognitive impairment with suspected nonamyloid pathology (SNAP): Prediction of progression

Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods: We measured markers of amyloid pathology (CSF b-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [¹⁸F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A-/A+ and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases. Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A-N+ and A+N+ groups (p # 0.005). Hypometabolism in SNAP patients was comparable to A1N1 patients (p 5 0.154), while hippocampal atrophy was more severe in SNAP patients (p 5 0.002). Compared with A+N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio 5 2.7 and 3.8, p 5 0.016 and p , 0.001), while A+N- patients did not (hazard ratio 5 1.13, p 5 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r 5 0.42, p 5 0.073). Conclusions: Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.