Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease.
We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD.
Salmon
Eric
E
Cyclotron Research Centre, University of Liege, Liege, Belgium. eric.salmon@ulg.ac.be
Perani
Daniela
D
Herholz
Karl
K
Marique
Patricia
P
Kalbe
Elke
E
Holthoff
Vjera
V
Delbeuck
Xavier
X
Beuthien-Baumann
Bettina
B
Pelati
Oriana
O
Lespagnard
Solange
S
Collette
Fabienne
F
Garraux
Gaëtan
G
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology* / Q000523:psychology; D001364:Awareness / Q000502:physiology; D017028:Caregivers; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D012647:Self-Assessment; D011795:Surveys and Questionnaires
D019788:Fluorodeoxyglucose F18