Journal
JOURNAL OF INTERNAL MEDICINE
Volume 278, Issue 3, Pages 277-290Publisher
WILEY
DOI: 10.1111/joim.12358
Keywords
Alzheimer's disease; frontal atrophy; medial temporal atrophy; mild cognitive impairment; posterior atrophy; visual rating scales
Categories
Funding
- InnoMed, an Integrated Project - European Union [FP6-2004-LIFE-SCIHEALTH-5]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Canadian Institutes of Health Research
- National Institutes of Health (NIH) [U01 AG024904]
- NIH [P30 AG010129, K01 AG030514]
- Kuopio University Hospital
- National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health
- NIHR Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust
- Institute of Psychiatry, Kings College London, UK
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BioClinica Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Co.
- Eisai Inc.
- Elan Pharmaceuticals Inc.
- Eli Lilly and Co.
- F. Hoffmann-La Roche Ltd and its affiliated company Genentech Inc.
- GE Healthcare
- Innogenetics NV
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Medpace Inc.
- Merck Co. Inc.
- Meso Scale Diagnostics LLC
- NeuroRx Research
- Novartis Pharmaceuticals Corp.
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- National Institute for Health Research [NF-SI-0512-10053] Funding Source: researchfish
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BackgroundAtrophy in the medial temporal lobe, frontal lobe and posterior cortex can be measured with visual rating scales such as the medial temporal atrophy (MTA), global cortical atrophy - frontal subscale (GCA-F) and posterior atrophy (PA) scales, respectively. However, practical cut-offs are urgently needed, especially now that different presentations of Alzheimer's disease (AD) are included in the revised diagnostic criteria. AimsThe aim of this study was to generate a list of practical cut-offs for the MTA, GCA-F and PA scales, for both diagnosis of AD and determining prognosis in mild cognitive impairment (MCI), and to evaluate the influence of key demographic and clinical factors on these cut-offs. MethodsAddNeuroMed and ADNI cohorts were combined giving a total of 1147 participants (322 patients with AD, 480 patients with MCI and 345 control subjects). The MTA, GCA-F and PA scales were applied and a broad range of cut-offs was evaluated. ResultsThe MTA scale showed better diagnostic and predictive performances than the GCA-F and PA scales. Age, apolipoprotein E (ApoE) epsilon 4 status and age at disease onset influenced all three scales. For the age ranges 45-64, 65-74, 75-84 and 85-94years, the following cut-offs should be used. MTA: 1.5, 1.5, 2 and 2.5; GCA-F, 1, 1, 1 and 1; and PA, 1, 1, 1 and 1, respectively, with an adjustment for early-onset ApoE epsilon 4 noncarrier AD patients (MTA: 2, 2, 3 and 3; and GCA-F: 1, 1, 2 and 2, respectively). ConclusionsIf successfully validated in clinical settings, the list of practical cut-offs proposed here might be useful in clinical practice. Their use might also (i) promote research on atrophy subtypes, (ii) increase the understanding of different presentations of AD, (iii) improve diagnosis and prognosis and (iv) aid population selection and enrichment for clinical trials.
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