A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease

Shinno, Hideto; Inagaki, Takuji; Miyaoka, Tsuyoshi; Okazaki, Shihoh; Kawamukai, Tetsuya; Utani, Etsuko; Inami, Yasushi; Horiguchi, Jun

doi:10.1016/j.jns.2007.04.017

Cited by 41 publications

(22 citation statements)

References 33 publications

(37 reference statements)

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“…In a post-mortem magnetic resonance spectroscopy study, they found that AD patients with psychosis had greater neuropil disruption in multiple brain regions, including the dorsolateral prefrontal cortex, superior temporal gyrus and inferior parietal cortex. Similar accelerated biomarker changes have been shown in the anterior cingulate gyrus of AD patients with delusions compared to those without delusions [35]. The fact that AD patients with delusions had significantly worse functional performance in this study compared to those without delusions has implications for clinical care.…”

Section: Discussionsupporting

confidence: 82%

Delusions Increase Functional Impairment in Alzheimers Disease

Fischer¹,

Ismail

Schweizer

2012

Dement Geriatr Cogn Disord

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Background/Aims: Delusions in Alzheimer’s disease (AD) may be associated with functional impairment. No studies to date have used functional instruments sensitive to changes in frontal executive function, possibly underestimating the impact. Methods: Patients with AD with and without delusions were administered cognitive tests and questionnaires to assess depression and quality of life. Caregivers were administered questionnaires to assess functional impairment, caregiver burden and behavioural symptoms. Results: AD patients with delusions (n = 19) when compared to AD patients without delusions (n = 19) matched for age, education and global cognitive function were significantly more functionally impaired based on performance on the Disability Assessment for Dementia Scale (p < 0.005). Conclusion: AD patients with delusions have significantly worse functional performance.

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Section: Discussionsupporting

confidence: 82%

Delusions Increase Functional Impairment in Alzheimers Disease

Fischer¹,

Ismail

Schweizer

2012

Dement Geriatr Cogn Disord

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“…The authors concluded that this latter group (termed as asymptomatic AD) with marked neuronal hypertrophy (in the hippocampus, ACC, and PCC) might account for the functional compensation reflected in the different clinical outcome compared to mild cognitive impairment and AD subgroups. Interestingly, a recent 1 H-MRS study (Shinno et al 2007) found that an increase in NAA in the ACC might protect Alzheimer's disease patients from developing behavioral and psychological symptoms. The study demonstrated that the neuropsychological scores (on a fourpoint scale of increasing severity) obtained in two categories of BEHAVE-AD (delusional thought and activity disturbance) were negatively related to NAA/Cr in the ACC, but not in the posterior cingulate gyrus.…”

Section: Discussionmentioning

confidence: 99%

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

Chiu

Mak

Yau

et al. 2013

AGE

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Magnetic resonance spectroscopy (MRS) can explore aging at a molecular level. In this study, we investigated the relationships between regional concentrations of metabolites (such as choline, creatine, myo-inositol, and N-acetyl-aspartate) and normal aging in 30 cognitively normal subjects (15 women and 15 men, age range 22-82, mean=49.9±18.3 years) using quantitative proton magnetic resonance spectroscopy. All MR scans were performed using a 3 T scanner. Point resolved spectroscopy was used as the volume selection method for the region-of-interest and the excitation method for water suppression. Single voxel spectroscopy with short echo time of 39 ms and repetition time of 2,000 ms was employed.Single voxels were placed in the limbic regions, i.e., anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and left and right hippocampi. Cerebrospinal fluid normalization and T1 and T2 correction factors were implemented in the calculation of absolute metabolite concentrations. A standardized T1W 3D volumetric fast field echo and axial T2-weighted fast spin-echo images were also acquired. Our results showed significant positive correlation of choline (r=0.545, p=0.002), creatine (r=0.571, p=0.001), and N-acetyl-aspartate (r= 0.674, p<0.001) in the ACC; choline (r=0.614, p< 0.001), creatine (r=0.670, p<0.001), and N-acetyl-aspartate (r=0.528, p=0.003) in the PCC; and NAA (r=0.409, p=0.025) in the left hippocampus, with age. No AGE (2014) significant gender effect on metabolite concentrations was found. In aging, increases in choline and creatine might suggest glial proliferation, and an increase in Nacetyl-aspartate might indicate neuronal hypertrophy. Such findings highlight the metabolic changes of ACC and PCC with age, which could be compensatory to an increased energy demand coupled with a lower cerebral blood flow.

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“…One can speculate that this greater disruption represents an acceleration of AD-related neurodegeneration. Proton magnetic resonance spectroscopy also allows the indirect measurement of AD pathology in living patients and has been used to implicate the anterior cingulate cortex (ACC) in patients with mild AD and delusions compared with those without delusions [32]. Delusional thinking was assessed in 30 AD patients using the BEHAVE-AD (Behavioral Pathology in Alzheimer's Disease) scale, and compared with AD-D patients (n=22), AD+D patients (n=8) had…”

Section: Neuropathologymentioning

confidence: 99%

Neurobiology of Delusions in Alzheimer’s Disease

Ismail

Nguyen

Fischer

et al. 2011

Curr Psychiatry Rep

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Alzheimer's disease (AD) is associated with cognitive and functional impairment as well as neuropsychiatric sequelae, including psychotic symptoms such as delusions and hallucinations. Strong evidence supports the need to study delusions separate from hallucinations. Integrating the epidemiology, clinical correlates, and neuropathological and genetic literature for delusions in AD allows us to speculate on etiology and mechanisms. Plaque and tangle deposition in individuals with susceptible alleles of serotonergic, muscarinic, nicotinic, or Apoε4 genes appears to result in disruption of cortical circuitry, culminating in delusions. While delusions in AD correspond to a phenotype distinct from AD without delusions, subtypes of delusions may also define further distinct clinical entities.Persecutory delusions may occur earlier in the illness and have a more significant genetic component than misidentification delusions, which are associated with increased cognitive impairment and advanced dementia. Clearly distinguishing between these two syndromes is essential to making progress in the area of delusions in AD.

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A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease

Abstract: We conclude that BPSD and the decline in cognitive function in AD might have separate pathologies.

Cited by 41 publications

References 33 publications

Delusions Increase Functional Impairment in Alzheimers Disease

Delusions Increase Functional Impairment in Alzheimers Disease

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

Neurobiology of Delusions in Alzheimer’s Disease

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A decrease in N-acetylaspartate and an increase in myoinositol in the anterior cingulate gyrus are associated with behavioral and psychological symptoms in Alzheimer's disease

Abstract: We conclude that BPSD and the decline in cognitive function in AD might have separate pathologies.

Cited by 41 publications

References 33 publications

Delusions Increase Functional Impairment in Alzheimers Disease

Delusions Increase Functional Impairment in Alzheimers Disease

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

Neurobiology of Delusions in Alzheimer’s Disease

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Delusions Increase Functional Impairment in Alzheimers Disease

Delusions Increase Functional Impairment in Alzheimers Disease