Academic journal article East Asian Archives of Psychiatry

Differences in Brain Metabolism Associated with Agitation and Depression in Alzheimer's Disease

Academic journal article East Asian Archives of Psychiatry

Differences in Brain Metabolism Associated with Agitation and Depression in Alzheimer's Disease

Article excerpt


The behavioural and psychological symptoms of dementia (BPSD) are common in patients diagnosed with Alzheimer's disease (AD) and responsible for substantial suffering endured by patients and caregivers. Although numerous studies have used neuroimaging techniques to investigate the relationship between BPSD and regional cerebral dysfunctions, no definite conclusions have been reached. (1-3) H-magnetic resonance spectroscopy (MRS) is a unique neuroimaging technique that enables measurement of several metabolites within a single examination. (4) The metabolite N-acetylaspartate-to-creatine (NAA/Cr) ratio is consistently lower in the MRS findings of patients with AD than in those of cognitively normal elderly people. (5,6) In contrast, the myo-inositol-to-Cr (mI/Cr) level is higher. Agitation and depression are among the most common BPSD in AD patients. Agitation occurs in 60% of patients, (7) whereas depression affects up to 50% of them. (8) Moreover, depression is a risk factor for dementia. (9) Lesion and imaging studies have suggested that frontal lobe dysfunction, particularly in the dorsolateral prefrontal cortex (DLPFC), is pathophysiologically linked to primary and secondary depression. (1,10,11) The findings from neuroimaging and pathological studies have also demonstrated frontal lobe involvement in AD patients who suffer from agitation. (3,12,13) The severity of agitation and aggression in AD patients was associated with an excessive atrophy of the frontal, insular, amygdala, cingulate, and hippocampal regions. (14) However, whether these findings are caused by the pathological changes in patients suffering from AD or by an independent event remains unknown. In this study, we employed [1.sup]H-MRS with the objective of determining the relationship between the regional changes of brain metabolites and BPSD in AD patients, by using the cingulate gyrus and the DLPFC as sites of interest.



We recruited 26 patients diagnosed with AD (14 women and 12 men; mean [+ or -] standard deviation [SD] age, 75 [+ or -] 9.3 years) from the memory clinic at the Taipei Veterans General Hospital. Diagnostic evaluation included a clinical interview, physical and neurological examinations, routine blood tests, an electroencephalogram, and a brain magnetic resonance imaging (MRI). All patients met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for probable AD. (15) The patients with substantial medical, neurological, and psychiatric diseases, but who were diagnosed as being free from AD were excluded from the study. The study protocol was approved by the Institutional Review Board of the Taipei Veterans General Hospital. After a complete description of the study to the patients or their legal guardians, all subjects provided written informed consent.

Neuropsychological Assessment

Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). (16) The severity levels of agitation and depression were assessed using the Cohen-Mansfield Agitation Inventory (17) (CMAI) and the Geriatric Depression Scale-Short Form (18) (GDS), respectively.

Cohen-Mansfield Agitation Inventory

The CMAI is composed of 29 descriptions of behavioural problems. Each item is scored according to the frequency of occurrence, ranging from 1 (never happens) to 7 (occurs several times in an hour). Scores on the scale, therefore, range from 29 to 203, with the higher scores representing increased frequency or numerous types of agitative behavioural problems.

Geriatric Depression Scale-Short Form

The GDS is a commonly used instrument for the assessment of depression, and consists of 15 questions, requiring "yes" or "no" answers. A higher score indicates more severe depression.

Magnetic Resonance Spectroscopy Study

Magnetic resonance image scans and spectroscopy were performed using a 1. …

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