Neural basis of three dimensions of agitated behaviors in patients with Alzheimer disease.

BACKGROUND: Agitated behaviors are frequently observed in patients with Alzheimer disease (AD). The neural substrate underlying the agitated behaviors in dementia is unclear. We hypothesized that different dimensions of agitated behaviors are mediated by distinct neural systems. METHODS: All the patients (n=32) underwent single photon emission computed tomography (SPECT). Using the Agitated Behavior in Dementia scale, we identified the relationships between regional cerebral blood flow (rCBF) patterns and the presence of each of three dimensions of agitated behavior (physically agitated behavior, verbally agitated behavior, and psychosis symptoms) in AD patients. Statistical parametric mapping (SPM) software was used to explore these neural correlations. RESULTS: Physically agitated behavior was significantly correlated with lower rCBF values in the right superior temporal gyrus (Brodmann 22) and the right inferior frontal gyrus (Brodmann 47). Verbally agitated behavior was significantly associated with lower rCBF values in the left inferior frontal gyrus (Brodmann 46, 44) and the left insula (Brodmann 13). The psychosis symptoms were significantly correlated with lower rCBF values in the right angular gyrus (Brodmann 39) and the right occipital lobe (Brodmann 19). CONCLUSION: Our results support the hypothesis that three different agitated behaviors may represent distinct neural networks in AD patients.

Reliability and validity of the Japanese version of the Agitated Behaviour in Dementia Scale in Alzheimer's disease: three dimensions of agitated behaviour in dementia.

BACKGROUND: Agitation in dementia seriously affects not only patients' quality of life (QOL), but also caregivers' QOL. Thus, an appropriate assessment of agitated behaviour in dementia is needed for clinical management. We developed the Japanese version of the Agitated Behaviour in Dementia scale (ABID), examined its reliability and validity, and carried out its factor analysis to elucidate its factor structure. METHODS: The Japanese version of the ABID was given caregivers of 149 Japanese patients with Alzheimer's disease (AD). The internal-consistency, test-retest reliability and concurrent validity of the Japanese version of the ABID were then examined. A factor analysis was used to examine the agitated behavioural dimensions underlying ABID. RESULTS: The Japanese version of the ABID showed an excellent internal reliability for both frequency ratings (Cronbach's α= 0.89) and reaction ratings (Cronbach's α= 0.92), and an excellent test-retest reliability for both frequency ratings and reaction ratings. The total score for the frequency ratings of the ABID was significantly associated with the Cohen-Mansfield Agitation Inventory (CMAI), and the total score for the reaction ratings of the ABID was significantly associated with the Zarit Burden Interview. The factor analysis showed three subtypes: physically agitated behaviour, verbally agitated behaviour and psychosis symptoms. CONCLUSIONS: The Japanese version of the ABID promises to be useful for assessing agitated behaviour in patients with AD. Importantly, understanding these subtypes of agitated behaviour might have implications for individualized treatment plans.

Upward shift of the pH optimum of Acremonium ascorbate oxidase.

A gene encoding a thermostable Acremonium ascorbate oxidase (ASOM) was randomly mutated to generate mutant enzymes with altered pH optima. One of the mutants, which exhibited a significantly higher activity in the pH range 4.5-7 compared to ASOM, had a Gln183Arg substitution in the region corresponding to SBR1, one of the substrate binding regions of the zucchini enzyme. The other mutant with almost the same pH profile as Gln183Arg had a Thr527Ala substitution near the type 3 copper center and became more sensitive to azide than ASOM. Site-directed mutagenesis in the substrate binding regions with reference to the amino acid sequences of plant enzymes led to isolation of mutants shifted upward in the pH optimum; Val193Pro and Val193Pro/Pro190Ile increased the pH optimum by 1 and 0.5 units, respectively, while retaining the near-wild-type thermostability and azide sensitivity. The homology model of ASOM constructed from the zucchini enzyme coordinates suggested that replacement of Val193 by Pro could disturb the ion pair networks among Arg309, Glu192, Arg194 and Glu311. This perturbation could affect either the molecular recognition between the substrate and ASOM or the electron transfer from the substrate to the type 1 copper center, leading to the alkaline shift of the catalytic activity of the mutant enzyme. The other mutations, Val193Pro/Pro190Ile, could also induce similar structural perturbations involving the ion pair networks.