title: A 'Disease Severity Index' to identify individuals with Subjective Memory Decline who will progress to mild cognitive impairment or dementia.
abstract: Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer's disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.
authors.affiliation: Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Farshad
authors.initials: F
authors.lastname: Falahati
authors.affiliation: Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Linden
authors.affiliation: Melbourne School of Psychological Sciences, University of Melbourne, Melbourne 3010, Australia.|The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3084, Australia.|Department of Neurology, Massachusetts General Hospital/Harvard Medical School, 02129 Boston, MA, USA.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Buckley
authors.affiliation: The Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3052, Australia.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.affiliation: ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, Sydney 2109, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Savage
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3084, Australia.|Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Australia.|Department of Medicine, Austin Health, University of Melbourne, Melbourne 3084, Australia.
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.affiliation: Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg 3084, Australia.|Department of Medicine, Austin Health, University of Melbourne, Melbourne 3084, Australia.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne 3084, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.|NIHR Biomedical Research Centre for Mental Health, London SE5 8AF, UK.|NIHR Biomedical Research Unit for Dementia, London SE5 8AF, UK.|Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Division of Clinical Geriatrics, Centre for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 141 86 Stockholm, Sweden.|Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: Eric
authors.initials: E
authors.lastname: Westman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D053327:Apolipoprotein E4