This proposal describes a plan to study lack of awareness of one's disabiltities, called anosognosia, in patients with dementia. Anosognosia contributes to patients'disabilities and frustrates families and caregivers. Lack of awareness may prevent patients from adhering to treatment recommendations, and causes them to pursue potentially risky behaviors that are beyond their limits, requiring supervision to ensure their safety. Although anosognoia is very common in Alzheimer's disease, it is even more common in Frontotemporal dementia, and the reasons for this are not clear. We have developed a model attempting to explain how anosognosia could develop from failures of specific cognitive abilities, including monitoring one's performance and emotion, and we have devised a plan to test whether these factors contribute to anosognosia, and whether the contributing factors differ in patients with Alzheimer's disease and Frontotemporal dementia. We will study 100 healthy older individuals, 50 patients with Alzheimer's disease, and 50 patients with Frontotemporal dementia. We will pursue the following specific aims: A) To define the relative contributions of performance monitoring, other frontal/executive functions, memory, and emotional reactivity to anosognosia in AD and FTD. We hypothesize that: 1) In FTD, performance monitoring and physiological activation during cognitive tasks will be correlated with anosognosia even after accounting for the contributions of memory and executive functions. 2) In AD, but not FTD, memory for recent performance on cognitive testing will make a significant contribution to anosognosia.;We hypothesize that 1) tissue loss in the right medial orbitofrontal cortex will predict physiological activation during testing, behavioral estimates of performance monitoring, and overall level of self-awareness in both FTD and AD [after controlling for the contributions of other relevant brain regions. 2) tissue loss in medial temporal regions (hippocampus, entorhinal cortex, parahippocampal gyrus) will significantly predict overall level of self awareness in AD, after the effects of medial OFC are taken into account.] To examine the relationship between performance monitoring, physiological activation, and anosognosia: We hypothesize that physiological activation during cognitive testing will correlate with behavioral measures of performance-monitoring (post-error slowing [and decreased FOK]) and with overall level of self- awareness across diagnostic groups. If these hypotheses are confirmed, we will have a much clearer idea of why patients with dementia are not aware of their deficits.

Public Health Relevance

Patients with dementia are usually unaware, or marginally aware of their thinking problems and the effects these deficits have on their life. This project will attempt to understand why patients with dementia have such poor awareness of their disability using cognitive tests developed by neuroscientists, and using brain imaging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Silverberg, Nina B
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Perry, David C; Datta, Samir; Sturm, Virginia E et al. (2017) Reward deficits in behavioural variant frontotemporal dementia include insensitivity to negative stimuli. Brain 140:3346-3356
Scherling, Carole S; Wilkins, Sarah E; Zakrezewski, Jessica et al. (2016) Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment. Front Aging Neurosci 8:120
Perry, David C; Sturm, Virginia E; Seeley, William W et al. (2014) Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia. Brain 137:1621-6
Rosen, Howard J; Alcantar, Oscar; Zakrzewski, Jessica et al. (2014) Metacognition in the behavioral variant of frontotemporal dementia and Alzheimer's disease. Neuropsychology 28:436-47
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Perry, David C; Lehmann, Manja; Yokoyama, Jennifer S et al. (2013) Progranulin mutations as risk factors for Alzheimer disease. JAMA Neurol 70:774-8
Chiao, Stephanie; Rosen, Howard J; Nicolas, Krista et al. (2013) Deficits in self-awareness impact the diagnosis of asymptomatic neurocognitive impairment in HIV. AIDS Res Hum Retroviruses 29:949-56
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Krueger, Casey E; Rosen, Howard J; Taylor, H Gerry et al. (2011) Know thyself: real-world behavioral correlates of self-appraisal accuracy. Clin Neuropsychol 25:741-56

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