Caroli Anna, Prestia Annapaola, Galluzzi Samantha, Ferrari Clarissa, van der Flier Wiesje M, Ossenkoppele Rik, Van Berckel Bart, Barkhof Frederik, Teunissen Charlotte, Wall Anders E, Carter Stephen F, Schöll Michael, Choo Il Han, Grimmer Timo, Redolfi Alberto, Nordberg Agneta, Scheltens Philip, Drzezga Alexander, Frisoni Giovanni B
From the Medical Imaging Unit (A.C.), Biomedical Engineering Department, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Bergamo; LENITEM-Laboratory of Epidemiology Neuroimaging and Telemedicine (A.P., S.G., C.F., A.R., G.B.F.), IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Alzheimer Center and Department of Neurology (W.M.v.d.F., R.O., P.S.), Department of Epidemiology & Biostatistics (W.M.v.d.F.), Department of Radiology & Nuclear Medicine (B.V.B., F.B.), and Neurochemistry Laboratorium and Biobank, Department of Clinical Chemistry (C.T.), VU University Medical Center, Amsterdam, the Netherlands; PET-Center (A.E.W.), Section of Nuclear Medicine & PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala University; Alzheimer Neurobiology Center (S.F.C., M.S., I.H.C., A.N.), Karolinska Institutet, Stockholm, Sweden; Wolfson Molecular Imaging Centre (S.F.C.), University of Manchester, UK; MedTech West (M.S.), Sahlgrenska University Hospital, University of Gothenburg, Sweden; Department of Neuropsychiatry (I.H.C.), School of Medicine, Chosun University, Gwangju, Republic of Korea; Department of Psychiatry and Psychotherapy (T.G.), Klinikum rechts der Isar, Technische Universitat Muenchen, Germany; Department of Geriatric Medicine (A.N.), Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Nuclear Medicine (A.D.), University of Cologne, Germany; and Departments of Internal Medicine and Psychiatry (G.B.F.), University Hospitals and University of Geneva, Switzerland.
Neurology. 2015 Feb 3;84(5):508-15. doi: 10.1212/WNL.0000000000001209. Epub 2015 Jan 7.
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).
We measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [(18)F]-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.
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).
Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
本研究旨在调查疑似非阿尔茨海默病病理（SNAP）和轻度认知障碍（MCI）患者认知功能进行性衰退的预测因素。
我们对201例MCI患者进行了长达6年的临床随访，检测其淀粉样蛋白病理标志物（脑脊液β淀粉样蛋白42）和神经退行性变标志物（MRI海马体积和[18F]氟脱氧葡萄糖PET皮质代谢），以检测认知功能的进行性衰退。我们根据是否存在淀粉样蛋白病理和神经退行性变将MCI患者分为A+/A-和N+/N-。SNAP为A-N+病例。
A-N-、A+N-、SNAP和A+N+组的病情进展者比例分别为11%（8/41）、34%（14/41）、56%（19/34）和71%（60/85）；APOE ε4携带者比例分别为29%、70%、31%和71%，SNAP组的比例与A+N-组和A+N+组均有显著差异（p≤0.005）。SNAP患者的代谢减退与A+N+患者相当（p = 0.154），而SNAP患者的海马萎缩更严重（p = 0.002）。与A-N-相比，SNAP和A+N+患者有认知功能进行性衰退的显著风险（风险比分别为2.7和3.8，p = 0.016和p < 0.001），而A+N-患者没有（风险比 = 1.13，p = 0.771）。在A+N-和A+N+组中，没有生物标志物能预测病情进展时间。在SNAP组中，病情进展时间越短与代谢减退越严重相关（r = 0.42，p = 0.073）。
我们的研究结果支持以下观点，即SNAP MCI患者具有特定的风险进展特征。
