Anna Caroli1, Annapaola Prestia1, Samantha Galluzzi1, Clarissa Ferrari1, Wiesje M van der Flier1, Rik Ossenkoppele1, Bart Van Berckel1, Frederik Barkhof1, Charlotte Teunissen1, Anders E Wall1, Stephen F Carter1, Michael Schöll1, Il Han Choo1, Timo Grimmer1, Alberto Redolfi1, Agneta Nordberg1, Philip Scheltens1, Alexander Drzezga1, Giovanni B Frisoni2. 1. 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. 2. 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. gfrisoni@fatebenefratelli.it.
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 [(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. 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.
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 [(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. 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.
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