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

Caroli, A.; Prestia, A.; Galluzzi, S.; Ferrari, C.; van der Flier, W. M.; Ossenkoppele, R.; Van Berckel, B.; Barkhof, F.; Teunissen, C.; Wall, A. E.; Carter, S. F.; Scholl, M.; Choo, I. H.; Grimmer, T.; Redolfi, A.; Nordberg, A.; Scheltens, P.; Drzezga, A.; Frisoni, G. B.; Stern, Yaakov; Alzheimer's Disease Neuroimaging Initiative

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 A1/A2 and N1/N2 based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A2N1 cases. Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A2N2, A1N2, SNAP, and A1N1, respectively; the proportion of APOE e4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A1N2 and A1N1 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 A2N2, SNAP and A1N1 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 A1N2 patients did not (hazard ratio 5 1.13, p 5 0.771). In A1N2 and A1N1 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. Neurology® 2015;84:508–515



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February 11, 2022