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Title: Atrophy, hypometabolism and clinical trajectories in patients with amyloid-negative Alzheimer’s disease
Austin Authors: Chételat, Gaël;Ossenkoppele, Rik;Villemagne, Victor L ;Perrotin, Audrey;Landeau, Brigitte;Mézenge, Florence;Jagust, William J;Dore, Vincent;Miller, Bruce L;Egret, Stéphanie;Seeley, William W;van der Flier, Wiesje M;La Joie, Renaud;Ames, David;van Berckel, Bart NM;Scheltens, Philip;Barkhof, Frederik;Rowe, Christopher C ;Masters, Colin L ;de La Sayette, Vincent;Bouwman, Femke;Rabinovici, Gil D
Affiliation: INSERM, U1077, Caen, France
Université de Caen Basse-Normandie UMR-S1077, Caen, France
Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France
CHU de Caen, Caen, France
VU University Medical Centre, Neuroscience Campus Amsterdam, Department of Neurology and Alzheimer Centre, Amsterdam, The Netherlands
VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands
University of California San Francisco, Memory and Aging Centre, Department of Neurology, San Francisco, CA, USA
Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Victoria, Australia
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA
Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Commonwealth Scientific Industrial Research Organization Health and Biosecurity Flagship, Herston, Queensland, Australia
VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam, The Netherlands
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia
National Ageing Research Institute, Parkville, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Mental Health, Parkville, Victoria, Australia
CHU de Caen, Service de Neurologie, Caen, France
Issue Date: Sep-2016 2016-06-29
Publication information: Brain 2016; 139(9): 2528-2539
Abstract: See O'Sullivan and Vann (doi:10.1093/aww166) for a scientific commentary on this article.About 15% of patients clinically diagnosed with Alzheimer's disease do not show high tracer retention on amyloid positon emission tomography imaging. The present study investigates clinical and demographic features, patterns of brain atrophy and hypometabolism and longitudinal clinical trajectories of these patients. Forty amyloid-negative patients carrying a pre-scan diagnosis of Alzheimer's disease dementia from four centres were included (11/29 females/males; mean age = 67 ± 9). Detailed clinical histories, including the clinical diagnoses before and after the amyloid scan and at follow-up, were collected. Patients were classified according to their pre-scan clinical phenotype as amnestic (memory predominant), non-amnestic (predominant language, visuospatial or frontal symptoms), or non-specific (diffuse cognitive deficits). Demographic, clinical, neuropsychological, magnetic resonance imaging and (18)F-fluorodeoxyglucose positon emission tomography data were compared to 27 amyloid-positive typical Alzheimer's disease cases (14/13 females/males; mean age = 71 ± 10) and 29 amyloid-negative controls (15/14 females/males; mean age = 69 ± 12) matched for age, gender and education. There were 21 amnestic, 12 non-amnestic, and seven non-specific amyloid-negative Alzheimer's disease cases. Amyloid-negative subgroups did not differ in age, gender or education. After the amyloid scan, clinicians altered the diagnosis in 68% of amyloid-negative patients including 48% of amnestic versus 94% of non-amnestic and non-specific cases. Amnestic amyloid-negative cases were most often reclassified as frontotemporal dementia, non-amnestic as frontotemporal dementia or corticobasal degeneration, and non-specific as dementia with Lewy bodies or unknown diagnosis. The longer-term clinical follow-up was consistent with the post-scan diagnosis in most cases (90%), including in amnestic amyloid-negative cases whose post-positon emission tomography diagnosis remained Alzheimer's disease. While the non-amnestic and non-specific amyloid-negative cases usually showed patterns of atrophy and hypometabolism suggestive of another degenerative disorder, the amnestic amyloid-negative cases had subtle atrophy and hypometabolism, restricted to the retrosplenial/posterior cingulate cortex. Patients with a negative amyloid positon emission tomography scan following an initial clinical diagnosis of Alzheimer's disease have heterogeneous clinical presentations and neuroimaging profiles; a majority showed a clinical progression that was consistent with a neurodegenerative condition. In contrast, in the subgroup of amnestic amyloid-negative cases, the clinical presentation and follow-up usually remained consistent with Alzheimer's disease. An alternative diagnosis was not made in about half of the amnestic amyloid-negative cases, highlighting the need for a clinical framework and terminology to define these patients, who may have underlying limbic-predominant, non-amyloid-related pathologies.
DOI: 10.1093/brain/aww159
ORCID: 0000-0003-3910-2453
PubMed URL:
Type: Journal Article
Subjects: Alzheimer’s disease
Retrosplenial posterior cingulate
Appears in Collections:Journal articles

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