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

Anna Caroli, Annapaola Prestia, Samantha Galluzzi, Clarissa Ferrari, Wiesje M. Van Der Flier, Rik Ossenkoppele, Bart Van Berckel, Frederik Barkhof, Charlotte Teunissen, Anders E. Wall, Stephen F. Carter, Michael Schöll, Il Han Choo, Timo Grimmer, Alberto Redolfi, Agneta Nordberg, Philip Scheltens, Alexander Drzezga, Giovanni B. Frisoni

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)508-515
Number of pages8
Issue number5
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Clinical Neurology


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