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Association between altered neurochemical metabolites and apathy in patients with Alzheimer's disease

Published online by Cambridge University Press:  16 November 2017

Yi-Chun Yeh ,
Chun-Wei Li ,
Yu-Ting Kuo ,
Mei-Feng Huang ,
Tai-Ling Liu ,
Twei-Shiun Jaw ,
Yi-Hsin Yang ,
Kuang-Che Kuo  and
Cheng-Sheng Chen
Yi-Chun Yeh
Affiliation:
Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Psychiatry, Kaohsiung Medical University Hospital, 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 Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Medical Imaging, Chi Mei Hospital, Tainan, Taiwan
Mei-Feng Huang
Affiliation:
Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Tai-Ling Liu
Affiliation:
Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Twei-Shiun Jaw
Affiliation:
Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Yi-Hsin Yang
Affiliation:
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Kuang-Che Kuo
Affiliation:
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Cheng-Sheng Chen*
Affiliation:
Department of Psychiatry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
*
Correspondence should be addressed to: Cheng-Sheng Chen, Professor, MD, PhD #100, Tzyou 1st Rd, Kaohsiung City, 807Taiwan. Phone: +886-7-3121101; Fax: +886-7-3134761. Email: [email protected].
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Abstract

Background:

Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS).

Methods:

Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed.

Results:

Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (β = −0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (β = −0.43, p = 0.028), behavior (β = −0.55, p = 0.002), and emotion (β = −0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region.

Conclusions:

Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.

Keywords

apathymagnetic resonance spectroscopyAlzheimer’s disease
Type
Research Article
Information
International Psychogeriatrics , Volume 30 , Issue 5: Issue Theme: Brain Imaging , May 2018 , pp. 761 - 768
Copyright
Copyright © International Psychogeriatric Association 2017 

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References

Aguero-Torres, H., Fratiglioni, L., Guo, Z., Viitanen, M., von Strauss, E. and Winblad, B. (1998). Dementia is the major cause of functional dependence in the elderly: 3-year follow-up data from a population-based study. American Journal of Public Health, 88, 1452–1456.Google Scholar
Aguero-Torres, H., Fratiglioni, L., Guo, Z., Viitanen, M. and Winblad, B. (1999). Mortality from dementia in advanced age: a 5-year follow-up study of incident dementia cases. Journal of Clinical Epidemiology, 52, 737–743. doi: 10.1016/S0895-4356(99)00067-0Google Scholar
Aguero-Torres, H., von Strauss, E., Viitanen, M., Winblad, B. and Fratiglioni, L. (2001). Institutionalization in the elderly: the role of chronic diseases and dementia. Cross-sectional and longitudinal data from a population-based study. Journal of Clinical Epidemiology, 54, 795–801. doi: 10.1016/S0895-4356(00)00371-1Google Scholar
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
Allman, J. M., Hakeem, A., Erwin, J. M., Nimchinsky, E. and Hof, P. (2001). The anterior cingulate cortex. The evolution of an interface between emotion and cognition. Annals of the New York Academy of Sciences, 935, 107–117. doi: 10.1111/j.1749-6632.2001.tb03476.xGoogle Scholar
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association.Google Scholar
Banerjee, S., Murray, J., Foley, B., Atkins, L., Schneider, J. and Mann, A. (2003). Predictors of institutionalisation in people with dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 74, 1315–1316.CrossRefGoogle ScholarPubMed
Bedford, S., Melzer, D. and Guralnik, J. (2001). Problem behavior in the last year of life: prevalence, risks, and care receipt in older Americans. Journal of the American Geriatrics Society, 49, 590–595. doi: 10.1046/j.1532-5415.2001.49119.xGoogle Scholar
Benoit, M. et al. (1999). Behavioral and psychological symptoms in Alzheimer's disease. Relation between apathy and regional cerebral perfusion. Dementia and Geriatric Cognitive Disorders, 10, 511–517.CrossRefGoogle ScholarPubMed
Benoit, M., Clairet, S., Koulibaly, P. M., Darcourt, J. and Robert, P. H. (2004). Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease. International Journal of Geriatric Psychiatry, 19, 864–869. doi: 10.1002/gps.1163Google 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. doi: 10.1016/S0149-7634(89)80048-XGoogle 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. doi: 10.1148/radiology.212.3.r99au35763Google 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. doi: 10.1016/S0730-725X(02)00512-XGoogle Scholar
Colombo, M., Vitali, S., Cairati, M., Vaccaro, R., Andreoni, G. and Guaita, A. (2007). Behavioral and psychotic symptoms of dementia (BPSD) improvements in a special care unit: a factor analysis. Archives of Gerontology and Geriatrics, 44 (Suppl. 1), 113–120. doi: 10.1016/j.archger.2007.01.017Google Scholar
Devinsky, O., Morrell, M. J. and Vogt, B. A. (1995). Contributions of anterior cingulate cortex to behaviour. Brain, 118, 279–306. doi: 10.1093/brain/118.1.279Google Scholar
Kantarci, K. (2007). 1H magnetic resonance spectroscopy in dementia. British Journal of Radiology, 80, S146–152. doi: 10.1259/bjr/60346217Google Scholar
Kato, T., Inubushi, T. and Kato, N. (1998). Magnetic resonance spectroscopy in affective disorders. Journal of Neuropsychiatry and Clinical Neurosciences, 10, 133–147. doi: 10.1176/jnp.10.2.133Google 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. doi: 10.1212/WNL.42.8.1578CrossRefGoogle Scholar
Lanctot, K. L. et al. (2007). A SPECT study of apathy in Alzheimer's disease. Dementia & Geriatric Cognitive Disorders, 24, 65–72.Google Scholar
Lanctôt, K. L. et al. (2007). A SPECT study of apathy in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 24, 65–72. doi: 10.1159/000103633Google Scholar
Landes, A. M., Sperry, S. D., Strauss, M. E. and DS, G. (2001). Apathy in Alzheimer's disease. Journal of the American Geriatrics Society, 49, 1700–1707.Google Scholar
Marin, R. S. (1990). Differential diagnosis and classification of apathy. American Journal of Psychiatry, 147, 22–30.Google Scholar
Marin, R. S. (1991). Apathy: a neuropsychiatric syndrome. Journal of Neuropsychiatry and Clinical Neurosciences, 3, 243–254. doi: 10.1176/jnp.3.3.243Google Scholar
Marin, R. S., Biedrzycki, R. C. and Firinciogullari, S. (1991). Reliability and validity of the apathy evaluation scale. Psychiatry Research, 38, 143–162. doi: 10.1016/0165-1781(91)90040-VGoogle Scholar
Marshall, G. A., Monserratt, L., Harwood, D., Mandelkern, M., Cummings, J. L. and Sultzer, D. L. (2007a). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Archives of Neurology, 64, 1015–1020.Google Scholar
Marshall, G. A., Monserratt, L., Harwood, D., Mandelkern, M., Cummings, J. L. and Sultzer, D. L. (2007b). Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Archives of Neurology, 64, 1015–1020. doi: 10.1001/archneur.64.7.1015Google Scholar
Matsumoto, N. et al. (2007). Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community. Dementia and Geriatric Cognitive Disorders, 23, 219–224. doi: 10.1159/000099472Google 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 & Associated Disorders, 9, 101–104.Google Scholar
Mega, M. S., Cummings, J. L., Fiorello, T. and Gornbein, J. (1996). The spectrum of behavioral changes in Alzheimer's disease. Neurology, 46, 130–135.Google Scholar
Migneco, O., Benoit, M. and PM, K. (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
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. doi: 10.1016/j.pneurobio.2006.12.003Google Scholar
Mori, T. et al. (2014). Apathy correlates with prefrontal amyloid beta deposition in Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 85, 449–455. doi: 10.1136/jnnp-2013-306110Google Scholar
Morris, J. C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 2412–2414.Google Scholar
Murman, D. L. and Colenda, C. C. (2005). The economic impact of neuropsychiatric symptoms in Alzheimer's disease: can drugs ease the burden? Pharmacoeconomics, 23, 227–242. doi: 10.2165/00019053-200523030-00004Google Scholar
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. doi: 10.1016/0720-048X(92)90226-YGoogle Scholar
Tekin, S. et al. (2001). Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease. Annals of Neurology., 49, 355–361. doi: 10.1002/ana.72Google Scholar
Teri, L. (1997). Behavior and caregiver burden: behavioral problems in patients with Alzheimer disease and its association with caregiver distress. Alzheimer Disease and Associated Disorders, 11 (Suppl. 4), S35–38.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. doi: 10.1212/WNL.56.5.592Google Scholar
Vilalta-Franch, J., Calvo-Perxas, L., Garre-Olmo, J., Turro-Garriga, O. and Lopez-Pousa, S. (2013). Apathy syndrome in Alzheimer's disease epidemiology: prevalence, incidence, persistence, and risk and mortality factors. Journal of Alzheimer's Disease, 33, 535–543. doi: 10.3233/jad-2012-120913Google Scholar
Yeh, Y. C. et al. (2014). Altered neurochemical metabolites in Alzheimer's disease patients with unawareness of deficits. International Psychogeriatrics, 26, 393–402. doi: 10.1017/s1041610213001944Google Scholar
Zanetti, O. et al. (1999). Insight in dementia: when does it occur? Evidence for a nonlinear relationship between insight and cognitive status. Journal of Gerontology: Psychological Sciences and The Journal of Gerontology: Social, 54, P100–106.Google Scholar