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Altered neurochemical metabolites in Alzheimer's disease patients with unawareness of deficits

Published online by Cambridge University Press:  28 November 2013

Yi-Chun Yeh ,
Cheng-Fang Yen ,
Chun-Wei Li ,
Yu-Ting Kuo ,
Chia-Hui Chen ,
Chen-Chang Lee ,
Gin-Chung Liu ,
Mei-Feng Huang ,
Tai-Ling Liu  and
Cheng-Sheng Chen
Yi-Chun Yeh
Affiliation:
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Cheng-Fang Yen*
Affiliation:
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Chun-Wei Li
Affiliation:
Department of Medical Imaging and Radiological Sciences, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
Yu-Ting Kuo
Affiliation:
Department of Medical Imaging and Radiological Sciences, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Medical Imaging, Chi Mei Medical Center, Tainan, Taiwan Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Chia-Hui Chen
Affiliation:
College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Chen-Chang Lee
Affiliation:
Department of Radiology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Taiwan
Gin-Chung Liu
Affiliation:
Department of Medical Imaging and Radiological Sciences, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Mei-Feng Huang
Affiliation:
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Tai-Ling Liu
Affiliation:
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Cheng-Sheng Chen*
Affiliation:
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
*
Correspondence should be addressed to: Cheng-Sheng Chen and Cheng-Feng Yen, Department of Psychiatry, Kaohsiung Medical University Hospital, #100, Tzyou 1st Rd, Kaohsiung City, Taiwan807. Phone: +886-7-312-1101, ext. 6816; Fax: +886-7-3134761. Email: sheng@kmu.edu.tw or chfaye@kmu.edu.tw.
Correspondence should be addressed to: Cheng-Sheng Chen and Cheng-Feng Yen, Department of Psychiatry, Kaohsiung Medical University Hospital, #100, Tzyou 1st Rd, Kaohsiung City, Taiwan807. Phone: +886-7-312-1101, ext. 6816; Fax: +886-7-3134761. Email: sheng@kmu.edu.tw or chfaye@kmu.edu.tw.
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Abstract

Background:

Unawareness of deficits is common and is associated with poor outcomes in Alzheimer's disease (AD); however, little is known about correlated neurobiochemical changes.

Methods:

Proton magnetic resonance spectroscopy was used to examine neurobiochemical correlates of unawareness of deficits as assessed by the Dementia Deficit Scale in 36 patients with AD. Magnetic resonance spectroscopy spectra were acquired from the anterior cingulate area and right orbitofrontal area. Concentrations of N-acetyl-aspartate (NAA), total creatine, and other neurometabolites were calculated.

Results:

Nineteen (52.8%) participants had relative unawareness of deficits. This condition was negatively correlated with NAA/creatine in the anterior cingulate area (β = −0.36, p = 0.025) and positively correlated with NAA/creatine in the right orbitofrontal area (β = 0.41, p = 0.009) after controlling for dementia severity.

Conclusions:

These findings suggest unawareness of deficits in AD was associated with the altered neurochemical metabolites in the anterior cingulate area and right orbitofrontal area. However, the two areas might have opposite neuronal functions in unawareness of deficits.

Keywords

unawareness of deficitsAlzheimer's diseasemagnetic resonance spectroscopyanterior cingulate areaorbitofrontal area
Type
Research Article
Information
International Psychogeriatrics , Volume 26 , Issue 3 , March 2014 , pp. 393 - 402
Copyright
Copyright © International Psychogeriatric Association 2013 

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References

Abe, N., Suzuki, M., Mori, E., Itoh, M. and Fujii, T. (2007). Deceiving others: distinct neural responses of the prefrontal cortex and amygdala in simple fabrication and deception with social interactions. Journal of Cognitive Neuroscience, 19, 287–295.CrossRefGoogle ScholarPubMed
Adalsteinsson, E., Sullivan, E. V., Kleinhans, N., Spielman, D. M. and Pfefferbaum, A. (2000). Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease. Lancet, 355, 1696–1697.CrossRefGoogle ScholarPubMed
Alexopoulos, G. S. (2002). The Cornell Scale for Depression in Dementia Administration & Scoring Guidelines. New York: Cornell Institute of Geriatric Psychiatry, Weill Medical College of Cornell University.Google Scholar
Amanzio, M. et al. (2011). Unawareness of deficits in Alzheimer's disease: role of the cingulate cortex. Brain, 134, 1061–1076.Google Scholar
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association.Google Scholar
Antoine, C., Antoine, P., Guermonprez, P. and Frigard, B. (2004). Awareness of deficits and anosognosia in Alzheimer's disease. Encephale, 30, 570–577. (In French)Google Scholar
Bates, T. E., Strangward, M., Keelan, J., Davey, G. P., Munro, P. M. and Clark, J. B. (1996). Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport, 7, 1397–1400.Google Scholar
Birken, D. L. and Oldendorf, W. H. (1989). N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neuroscience and Biobehavioral Reviews, 13, 23–31.Google Scholar
Botvinick, M. M. (2007). Conflict monitoring and decision making: reconciling two perspectives on anterior cingulate function. Cognitive, Affective & Behavioral Neuroscience, 7, 356–366.CrossRefGoogle ScholarPubMed
Braver, T. S., Barch, D. M., Gray, J. R., Molfese, D. L. and Snyder, A. (2001). Anterior cingulate cortex and response conflict: effects of frequency, inhibition and errors. Cerebral Cortex, 11, 825–836.Google Scholar
Bush, G., Luu, P. and Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4, 215–222.Google Scholar
Casey, B. J. et al. (1997). The role of the anterior cingulate in automatic and controlled processes: a developmental neuroanatomical study. Developmental Psychobiology, 30, 61–69.Google Scholar
Chan, S., Shungu, D. C., Douglas-Akinwande, A., Lange, D. J. and Rowland, L. P. (1999). Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology, 212, 763–769.Google Scholar
Cheng, L. L., Newell, K., Mallory, A. E., Hyman, B. T. and Gonzalez, R. G. (2002). Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology. Magnetic Resonance Imaging, 20, 527–533.Google Scholar
Clare, L., Wilson, B. A., Carter, G., Roth, I. and Hodges, J. R. (2002). Assessing awareness in early-stage Alzheimer's disease: development and piloting of the Memory Awareness Rating Scale. Neuropsychological Rehabilitation, 12, 341–362.Google Scholar
Derouesne, C., Thibault, S., Lagha-Pierucci, S., Baudouin-Madec, V., Ancri, D. and Lacomblez, L. (1999). Decreased awareness of cognitive deficits in patients with mild dementia of the Alzheimer type. International Journal of Geriatric Psychiatry, 14, 1019–1030.Google Scholar
Hanyu, H. et al. (2008). Neuroanatomical correlates of unawareness of memory deficits in early Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 25, 347–353.Google Scholar
Harada, T. et al. (2009). Neural correlates of the judgment of lying: a functional magnetic resonance imaging study. Neuroscience Research, 63, 24–34.Google Scholar
Howorth, P. and Saper, J. (2003). The dimensions of insight in people with dementia. Aging & Mental Health, 7, 113–122.CrossRefGoogle ScholarPubMed
Ito, A. et al. (2011). The role of the dorsolateral prefrontal cortex in deception when remembering neutral and emotional events. Neuroscience Research, 69, 121–128.Google Scholar
Jansen, J. F., Backes, W. H., Nicolay, K. and Kooi, M. E. (2006). 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology, 240, 318–332.Google Scholar
Jessen, F. et al. (2001). Decrease of N-acetylaspartate in the MTL correlates with cognitive decline of AD patients. Neurology, 57, 930–932.Google Scholar
Johnson, S. C., Baxter, L. C., Wilder, L. S., Pipe, J. G., Heiserman, J. E. and Prigatano, G. P. (2002). Neural correlates of self-reflection. Brain, 125, 1808–1814.Google Scholar
Kantarci, K. (2007). 1H magnetic resonance spectroscopy in dementia. British Journal of Radiology, 80, S146–152.Google Scholar
Kantarci, K. et al. (2007). Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease. Neurobiology of Aging, 28, 1330–1339.Google Scholar
Kantarci, K. et al. (2008). Alzheimer disease: postmortem neuropathologic correlates of antemortem 1H MR spectroscopy metabolite measurements. Radiology, 248, 210–220.Google Scholar
Kato, T., Inubushi, T. and Kato, N. (1998). Magnetic resonance spectroscopy in affective disorders. Journal of Neuropsychiatry and Clinical Neurosciences, 10, 133–147.Google Scholar
Klunk, W. E., Panchalingam, K., Moossy, J., McClure, R. J. and Pettegrew, J. W. (1992). N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer's disease brain: a preliminary proton nuclear magnetic resonance study. Neurology, 42, 1578–1585.Google Scholar
Krishnan, K. R. et al. (2003). Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease. American Journal of Psychiatry, 160, 2003–2011.CrossRefGoogle ScholarPubMed
Lissek, S. et al. (2008). Cooperation and deception recruit different subsets of the theory-of-mind network. PLoS One, 3, e2023.Google Scholar
MacQuarrie, C. R. (2005). Experiences in early stage Alzheimer's disease: understanding the paradox of acceptance and denial. Aging & Mental Health, 9, 430–441.Google Scholar
Mangone, C. A. et al. (1991). Impaired insight in Alzheimer's disease. Journal of Geriatric Psychiatry and Neurology, 4, 189–193.Google Scholar
Marshall, G. A., Monserratt, L., Harwood, D., Mandelkern, M., Cummings, J. L. and Sultzer, D. L. (2007). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Archives of Neurology, 64, 1015–1020.Google Scholar
McDaniel, K. D., Edland, S. D. and Heyman, A. (1995). Relationship between level of insight and severity of dementia in Alzheimer disease. CERAD Clinical Investigators. Consortium to Establish a Registry for Alzheimer's Disease. Alzheimer Disease and Associated Disorders, 9, 101–104.Google Scholar
McGlynn, S. M. and Schacter, D. L. (1989). Unawareness of deficits in neuropsychological syndromes. Journal of Clinical and Experimental Neuropsychology, 11, 143–205.Google Scholar
Michon, A., Deweer, B., Pillon, B., Agid, Y. and Dubois, B. (1994). Relation of anosognosia to frontal lobe dysfunction in Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 805–809.Google Scholar
Migliorelli, R. et al. (1995). Anosognosia in Alzheimer's disease: a study of associated factors. Journal of Neuropsychiatry and Clinical Neurosciences, 7, 338–344.Google Scholar
Migneco, O. et al. (2001). Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndrome: a study in Alzheimer's disease and nondemented patients. Neuroimage, 13, 896–902.Google Scholar
Miller, B. L., Moats, R. A., Shonk, T., Ernst, T., Woolley, S. and Ross, B. D. (1993). Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology, 187, 433–437.Google Scholar
Mimura, M. (2008). Memory impairment and awareness of memory deficits in early-stage Alzheimer's disease. Tohoku Journal of Experimental Medicine, 215, 133–140.Google Scholar
Modrego, P. J., Pina, M. A., Fayed, N. and Diaz, M. (2006). Changes in metabolite ratios after treatment with rivastigmine in Alzheimer's disease: a nonrandomised controlled trial with magnetic resonance spectroscopy. CNS Drugs, 20, 867–877.Google Scholar
Moffett, J. R., Ross, B., Arun, P., Madhavarao, C. N. and Namboodiri, A. M. (2007). N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Progress in Neurobiology, 81, 89–131.Google Scholar
Morris, J. C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 2412–2414.Google Scholar
Nakaaki, S. et al. (2008). Impact of depression on insight into memory capacity in patients with Alzheimer disease. Alzheimer Disease and Associated Disorders, 22, 369–374.CrossRefGoogle ScholarPubMed
Northoff, G., Bermpohl, F., Schoeneich, F. and Boeker, H. (2007). How does our brain constitute defense mechanisms? First-person neuroscience and psychoanalysis. Psychotherapy and Psychosomatics, 76, 141–153.Google Scholar
Okonkwo, O. C., Spitznagel, M. B., Alosco, M. L. and Tremont, G. (2010). Associations among measures of awareness of cognitive deficits in dementia. Alzheimer's & Dementia, 6, 312–318.Google Scholar
Pfefferbaum, A., Adalsteinsson, E., Spielman, D., Sullivan, E. V. and Lim, K. O. (1999). In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging. Magnetic Resonance in Medicine, 41, 276–284.Google Scholar
Reed, B. R., Jagust, W. J. and Coulter, L. (1993). Anosognosia in Alzheimer's disease: relationships to depression, cognitive function, and cerebral perfusion. Journal of Clinical and Experimental Neuropsychology, 15, 231–244.Google Scholar
Ries, M. L. et al. (2007). Anosognosia in mild cognitive impairment: relationship to activation of cortical midline structures involved in self-appraisal. Journal of the International Neuropsychological Society, 13, 450–461.CrossRefGoogle ScholarPubMed
Ross, B. D. (1991). Biochemical considerations in 1H spectroscopy. Glutamate and glutamine; myo-inositol and related metabolites. NMR in Biomedicine, 4, 59–63.Google Scholar
Ross, B., Kreis, R. and Ernst, T. (1992). Clinical tools for the 90s: magnetic resonance spectroscopy and metabolite imaging. European Journal of Radiology, 14, 128–140.CrossRefGoogle ScholarPubMed
Salmon, E. et al. (2006). Neural correlates of anosognosia for cognitive impairment in Alzheimer's disease. Human Brain Mapping, 27, 588–597.Google Scholar
Schmitz, T. W., Rowley, H. A., Kawahara, T. N. and Johnson, S. C. (2006). Neural correlates of self-evaluative accuracy after traumatic brain injury. Neuropsychologia, 44, 762–773.Google Scholar
Shibata, K., Narumoto, J., Kitabayashi, Y., Ushijima, Y. and Fukui, K. (2008). Correlation between anosognosia and regional cerebral blood flow in Alzheimer's disease. Neuroscience Letters, 435, 7–10.Google Scholar
Snow, A. L., Norris, M. P., Doody, R., Molinari, V. A., Orengo, C. A. and Kunik, M. E. (2004). Dementia Deficits Scale. Rating self-awareness of deficits. Alzheimer Disease and Associated Disorders, 18, 22–31.Google Scholar
Starkstein, S. E., Sabe, L., Chemerinski, E., Jason, L. and Leiguarda, R. (1996). Two domains of anosognosia in Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 61, 485–490.Google Scholar
Thompson, C. and Spilsbury, K. (2007). WITHDRAWN: Support for carers of people with Alzheimer's type dementia. Cochrane Database Systemic Review, 18, CD000454.Google Scholar
Trouillet, R., Gely-Nargeot, M. C. and Derouesne, C. (2003). Unawareness of deficits in Alzheimer's disease: a multidimentional approach. Psychologie & Neuropsychiatrie du Vieillissement, 1, 99–110. (In French)Google Scholar
Urenjak, J., Williams, S. R., Gadian, D. G. and Noble, M. (1993). Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. Journal of Neuroscience, 13, 981–989.Google Scholar
Valenzuela, M. J. and Sachdev, P. (2001). Magnetic resonance spectroscopy in AD. Neurology, 56, 592–598.Google Scholar
Vogel, A., Hasselbalch, S. G., Gade, A., Ziebell, M. and Waldemar, G. (2005). Cognitive and functional neuroimaging correlate for anosognosia in mild cognitive impairment and Alzheimer's disease. International Journal of Geriatric Psychiatry, 20, 238–246.Google Scholar
Yang, Y. et al. (2007). Localisation of increased prefrontal white matter in pathological liars. British Journal of Psychiatry, 190, 174–175.Google Scholar
Zanetti, O. et al. (1999). Insight in dementia: when does it occur? Evidence for a nonlinear relationship between insight and cognitive status. Journals of Gerontology. Series B, Psychological Sciences and Social Sciences, 54, P100–106.Google Scholar