title: Memory self-awareness in the preclinical and prodromal stages of Alzheimer's disease.
abstract: While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer's disease dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the preclinical and prodromal stages of the disease. Paradoxically, very early in the Alzheimer's disease process, individuals may experience heightened awareness of memory changes before any objective cognitive deficits can be detected, here referred to as hypernosognosia. In contrast, awareness of memory dysfunction shown by individuals with mild cognitive impairment (MCI) is very variable, ranging from marked concern to severe lack of insight. This study aims at improving our mechanistic understanding of how alterations in memory self-awareness are related to pathological changes in clinically normal (CN) adults and MCI patients. 297 CN and MCI patients underwent PiB-PET (Positron Emission Tomography using Pittsburgh Compound B) in vivo amyloid imaging. Amyloid burden was estimated from Alzheimer's disease vulnerable regions, including the frontal, lateral parietal and lateral temporal, and retrosplenial cortex. Memory self-awareness was assessed using discrepancy scores between subjective and objective measures of memory function. A set of univariate analysis of variance were performed to assess the relationship between self-awareness of memory and amyloid pathology. Whereas CN individuals harboring amyloid pathology demonstrated hypernosognosia, MCI patients with increased amyloid pathology demonstrated anosognosia. In contrast, MCI patients with low amounts of amyloid were observed to have normal insight into their memory functions. Altered self-awareness of memory tracks with amyloid pathology. The findings of variability of awareness may have important implications for the reliability of self-report of dysfunction across the spectrum of preclinical and prodromal Alzheimer's disease.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: patrizia@nmr.mgh.harvard.edu.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vannini
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Amariglio
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Radiology, Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Cliniques Universitaires Saint-Luc, Institute of Neurosciences, Université Catholique de Louvain, 10 Av. Hippocrate, 1200 Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Hanseeuw
authors.affiliation: Department of Radiology, Division of Molecular Imaging and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Biospective, Inc., Montreal, Canada.
authors.forename: Donald G
authors.initials: DG
authors.lastname: McLaren
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jasmeer
authors.initials: J
authors.lastname: Chhatwal
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation and Cognitive Neurology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Dorene
authors.initials: D
authors.lastname: Rentz
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001364:Awareness; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000523:psychology*; D017281:Cost of Illness; D003430:Cross-Sectional Studies; D059026:Diagnostic Self Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory; D000073216:Mental Status and Dementia Tests; D008875:Middle Aged; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D019275:Radiopharmaceuticals; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D013844:Thiazoles
keywords: Amyloid; Anosognosia; Hypernosognosia; Metamemory; Mild Cognitive Impairment