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Abstract
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 β-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 A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A−N−, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N− patients did not (hazard ratio = 1.13, p = 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 = 0.42, p = 0.073).
Conclusions: Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
GLOSSARY
- Aβ=
- β-amyloid;
- Aβ42=
- β-amyloid 1–42;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- EU=
- European Union;
- FDG=
- [18F]-fluorodeoxyglucose;
- FTD=
- frontotemporal dementia;
- KUHH=
- Karolinska University Hospital Huddinge;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- MUCH=
- Klinikum rechts der Isar der Technischen Universität München;
- SNAP=
- suspected non–Alzheimer disease pathology;
- TOMC=
- Translational Outpatient Memory Clinic;
- VUMC=
- VU University Medical Center
Footnotes
A portion of the data used in preparation of this article was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The ADNI investigators contributed to the design and implementation of ADNI and/or provided data. The ADNI list is available on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received April 30, 2014.
- Accepted in final form October 8, 2014.
- © 2015 American Academy of Neurology
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