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Brain Regions Associated with Anosognosia for Memory Disturbance in Alzheimer’S Disease: a Magnetic Resonance Imaging Study

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Brain Regions Associated with Anosognosia for Memory Disturbance in Alzheimer’S Disease: a Magnetic Resonance Imaging Study Journal name: Neuropsychiatric Disease and Treatment Article Designation: Original Research Year: 2017 Volume: 13 Neuropsychiatric Disease and Treatment Dovepress Running head verso: Fujimoto et al Running head recto: Brain regions associated with anosognosia in AD open access to scientific and medical research DOI: http://dx.doi.org/10.2147/NDT.S139177 Open Access Full Text Article ORIGINAL RESEARCH Brain regions associated with anosognosia for memory disturbance in Alzheimer’s disease: a magnetic resonance imaging study Hiroshi Fujimoto1 Background and objective: Patients with Alzheimer’s disease (AD) are frequently unaware Teruyuki Matsuoka1 of their cognitive symptoms and medical diagnosis. The term “anosognosia” is used to indi- Yuka Kato1 cate a general lack of awareness of one’s disease or disorder. The neural substrate underlying Keisuke Shibata1 anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial Kaeko Nakamura1 sign of AD, it is important to determine the neural correlates. This study was designed to Kei Yamada2 investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD. Jin Narumoto1 Methods: The subjects were 49 patients with mild AD who participated in a retrospective 1 Department of Psychiatry, Graduate cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, School of Medical Science, Kyoto For personal use only. Prefectural University of Medicine, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Kyoto, Japan; 2Department of Anosognosia for memory disturbance was assessed based on the discrepancy between question- Radiology, Graduate School of Medical naire scores of patients and their caregivers. Structural MRI data were analyzed to explore the Science, Kyoto Prefectural University of Medicine, Kyoto, Japan association between anosognosia and brain atrophy, using a voxel-based approach. Statisti- cal parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates. Results: The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus. Conclusion: The left superior frontal gyrus was involved in anosognosia for memory dis- turbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 137.108.70.14 on 16-Jan-2020 anosognosia in mild AD. Keywords: anosognosia, Alzheimer’s disease, MRI, superior frontal gyrus Introduction Patients with neurological disorders are frequently unaware of their cognitive and behavioral symptoms. The term “anosognosia” was originally used by Babinski in 1914 to describe patients with lack of awareness of hemiplegia, but now is used to Correspondence: Teruyuki Matsuoka Department of Psychiatry, Graduate denote general unawareness of one’s disease or impairments. Anosognosia is a common School of Medical Science, Kyoto symptom in patients with Alzheimer’s disease (AD)1,2 and affects treatment and care Prefectural University of Medicine, of AD. From a clinical perspective, anosognosia in AD is associated with psychiatric 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602–8566, Japan symptoms, behavioral disturbances, and caregiver burden.3,4 Tel +81 75 251 5612 In the early stages of AD, most patients have some insight into their cognitive Fax +81 75 251 5839 Email [email protected] dysfunction. However, as the disease progresses, the consciousness of disease often submit your manuscript | www.dovepress.com Neuropsychiatric Disease and Treatment 2017:13 1753–1759 1753 Dovepress © 2017 Fujimoto et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/NDT.S139177 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Powered by TCPDF (www.tcpdf.org) 1 / 1 Fujimoto et al Dovepress disappears and patients may become indifferent to their was approved by the Ethics Committee of Kyoto Prefectural clinical condition.1,5,6 AD patients with anosognosia cannot University of Medicine. Since this study was a retrospective recognize a lack or absence of insight in impairments of study, a requirement for written informed consent was waived activities of daily living (ADL) or cognitive dysfunction, par- by the ethics committee. Instead of written informed consent, ticularly in the memory domain.7 Anosognosia for memory information on this study was made available in the waiting disturbance occurs about 2–3 years before dementia onset,8 room of our outpatient clinic and on our institutional home indicating that anosognosia might be an early sign of AD. page. In addition, information on the right to opt out of the The brain substrates in anosognosia in AD have not study was also presented. If the subjects hoped to opt out of been fully determined. Neuroimaging studies using fluoro- the study, the subjects were excluded from this study. deoxyglucose positron emission tomography, single photon emission computed tomography (SPECT), and functional Quantitative assessment of anosognosia magnetic resonance imaging (fMRI) have shown a relation- for memory disturbance ship between anosognosia for memory disturbance in AD and All patients were given a questionnaire adapted from Squire dysfunction in the frontal and temporoparietal regions.9–19 To and Zouzounis.22 The anosognosia score was calculated as our knowledge, the structural brain substrates of anosognosia described in a previous study.23 The questionnaire includes for memory disturbance in AD have not been examined. 20 items reflecting different aspects of memory function. Since anosognosia for memory disturbance might be an Patients and caregivers rated each item separately using a early sign of AD, it is important to define the neural corre- 9-point scale from -4 (worst) to +4 (best) for comparison lates. Therefore, the objective of this study is to investigate of the patient’s current ability level to that of 5 years ago. the structural neural correlates of anosognosia for memory Therefore, the total scores range from -80 to +80. To derive disturbance in mild AD, using MRI. the anosognosia score, the total caregiver score was sub- tracted from the total patient score. The resulting anosognosia Methods score could range from -160 to +160, with a higher score For personal use only. Participants indicating less awareness of memory deficits. These scores The subjects were 49 patients (16 males and 33 females) have previously been shown to be reliable in patients with who visited the Center for Diagnosis of Dementia at Kyoto dementia.1,24–26 Prefectural University of Medicine and were diagnosed with AD, based on National Institute of Neurological and Com- Cognitive and neuropsychiatric municative Disorders and Stroke-Alzheimer’s Disease and assessments Related Disorders Association criteria for probable AD.20 To The MMSE and Clinical Dementia Rating27,28 were used for ascertain the diagnosis of AD, all the subjects were assessed assessment of global cognitive deficits and severity of dementia. comprehensively by geriatric psychiatrists using medical Psychiatric symptoms were assessed with the Neuropsychiatric and social histories, physical and neurological examina- Inventory (NPI), on which the greater the score, the higher tions, neuropsychological tests, laboratory data, and brain would be the severity or frequency.29,30 The NPI evaluates 12 Neuropsychiatric Disease and Treatment downloaded from https://www.dovepress.com/ by 137.108.70.14 on 16-Jan-2020 imaging. Only patients with mild AD, defined by a score neuropsychiatric symptoms in dementia: delusions, hallucina- of $17 on the mini mental state examination (MMSE),21 tions, agitation, depression, anxiety, euphoria, apathy, disinhibi- were included in the study. Patients with a significant history tion, irritability, aberrant motor behavior, sleep disturbance, and of psychiatric or neurological disorders, including stroke, eating problems. The Geriatric Depression Scale (GDS) is a head injury, epilepsy, psychiatric disorders, alcohol abuse, self-rating scale with 15 questions for depression,31,32 on which evidence of use of psychoactive substances, or a serious the higher the score, the more the severity of depression. medical condition were excluded. None of the subjects had been treated with cholinesterase inhibitors, memantine, or Magnetic resonance imaging acquisition psychotropic drugs because our center examines patients and analysis without a diagnosis. All subjects underwent assessment of MRI was performed on a 3.0T clinical scanner with an 8-channel anosognosia,
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