Development of a novel convenient Alzheimer's disease assessment scale, the ABC Dementia Scale, using item response theory.

AIM: The present study aimed to assess the interrater reliability and construct the validity of a novel, convenient informant-based Alzheimer's disease assessment scale to prepare its final version. METHODS: For the assessment, site investigators, co-medicals and, if available, medical staff other than doctors or co-medicals interviewed study informants to assess individuals using this scale. We then analyzed the interrater reliability and construct validity using factor analysis and item response characteristics. RESULTS: In this study, 427 eligible participants were enrolled. We first examined the interrater reliability, and found that the lower limit of the confidence interval of each item was never <0.4 (except for the item "delusion of theft"). After deleting this item, the 14 items of this scale were organized into three domains (activities of daily living, behavioral and psychological symptoms of dementia, and cognitive function) through factor analysis. After discussion of the similarity of two items and their integration into one item, we confirmed that the final version of the 13-item scale showed almost the same degree of interrater reliability and construct validity as the former version of this scale. CONCLUSIONS: The final version of this novel Alzheimer's disease assessment scale had high interrater reliability and construct validity. We named it the ABC (activities of daily living, behavioral and psychological symptoms of dementia, and cognitive function) Dementia Scale. Further studies on its validation are required. Geriatr Gerontol Int 2019; 19: 18-23.

ABC Dementia Scale: A Quick Assessment Tool for Determining Alzheimer's Disease Severity.

BACKGROUND: In this study, we examined the construct validity, concurrent validity concerning other standard scales, intrarater reliability, and changes in scores at 12 weeks of the previously developed ABC Dementia Scale (ABC-DS), a novel assessment tool for Alzheimer's disease (AD). METHODS: Data were obtained from 312 patients diagnosed with either AD or mild cognitive impairment. The scores on the ABC-DS and standard scales were compared. RESULTS: The 13 items of the ABC-DS are grouped into three domains, and the domain-level scores were highly correlated with the corresponding conventional scales. Statistically significant changes in assessment scores after 12 weeks were observed for the total ABC-DS scores. CONCLUSION: Our results demonstrate the ABC-DS to have good validity and reliability, and its usefulness in busy clinical settings.

Serotonin transporter gene polymorphism and BPSD in mild Alzheimer's disease.

The purpose of the present study was to confirm an association of functional polymorphism within the serotonin transporter (5-HTT) gene with Alzheimer's disease (AD) and behavioral and psychological symptoms of dementia (BPSD) in mild AD. Apolipoprotein E (ApoE) gene polymorphism and 2 types of functional polymorphism in the 5-HTT gene, 5-HTT-linked polymorphic region (5-HTTLPR) and a 5-HTT variable number of tandem repeats sequence (5-HTTVNTR) were analyzed longitudinally in outpatients with mild AD to find out whether there was a relation between any such polymorphisms and the occurrence of BPSD. No significant differences in genotype distribution or allele frequencies were identified for 5-HTTLPR or 5-HTTVNTR between AD patients and age- and sex-matched non-demented controls regardless of ApoE epsilon4 allele. No significant differences were noted in 5-HTTLPR genotype or allele distributions between AD patients with or without BPSD. However, significant associations were observed between presence of 5-HTTVNTR allele 10 and BPSD or aggressiveness. This difference was independent of the presence of the ApoE epsilon4 allele. As a result, 5-HTT polymorphisms are unlikely to play any substantial role in susceptibility to AD. Conversely, 5-HTTVNTR influences the risk of developing BPSD or aggressiveness and genetic variations in the 5-HTT gene may be involved in the development of symptomatology for mild AD.

Reduced prepulse inhibition in rats with entorhinal cortex lesions.

The relationship between the entorhinal cortex and prepulse inhibition (PPI) as well as dopaminergic participation in this relationship were examined. PPI is an operational measure of sensorimotor gating in which a robust response to a startling auditory pulse stimulus is inhibited when the stimulus is preceded by a weak prepulse. PPI can be measured in various species and is reduced in several neuropsychiatric disorders and in dopamine-activated rats. The entorhinal cortex was damaged bilaterally using ibotenic acid, and acoustic startle experiments were performed during treatment with haloperidol or saline on day 21 after the ibotenic acid injection. Neither this injection nor haloperidol affected the amplitude of the startle movement. Bilateral entorhinal cortex lesions reduced PPI, while haloperidol partially restored it. The entorhinal cortex and the sensorimotor gating system therefore may be related via dopaminergic circuits, possibly including the nucleus accumbens. Further, as the entorhinal cortex provides the major extrinsic synaptic input to the rat hippocampus, disease involvement of this region may severely affect cognition in various disorders including schizophrenia.

[A study of the effect of donepezil hydrochloride on cognitive function in patients with dementia of Alzheimer's type using WAIS-R].

The present study aimed to assess the initial effects of donepezil hydrochloride (DPZ) on various aspects of cognitive function in patients with dementia of Alzheimer's type (DAT) using the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). DPZ was administered to 47 patients with mild-to-moderate DAT (D group). The control group comprised 61 patients who had been followed up before DPZ was released for use (C group). Both groups underwent WAIS-R testing, before and after 10 months of treatment with DPZ for group D, and at time of diagnosis of DAT and 10 months later for group C. D and C groups did not differ significantly in terms of gender ratio, years of education, age at onset of DAT, age at administration of DPZ or at diagnosis of DAT, severity of dementia, MMSE score, presence of behavioral and psychological symptoms of dementia, concomitant use of psychotropic medication, or initiation of rehabilitation. No significant differences were found between D and C groups in verbal (V), performance (P) or full-scale (F) intelligence quotient (IQ), or in six verbal subtest scores of VIQ and five performance subtest scores of PIQ on WAIS-R, before administration of DPZ or at diagnosis of DAT. For differences between each score on WAIS-R at diagnosis of DAT or before administration of DPZ and 10 months later, DPZ inhibited decreases in FIQ and in VIQ, PIQ, vocabulary, similarities, picture arrangement and object assembly subtest scores on WAIS-R. These indices are related to concept formation and abstract thinking, which form part of executive function. DPZ effectively prevented decline of cognitive function, particularly executive function, in patients with DAT.

Dopamine D3 receptor gene polymorphism influences on behavioral and psychological symptoms of dementia (BPSD) in mild dementia of Alzheimer's type.

Dopamine D3 receptor (DRD3) is present in the limbic system, which is thought to regulate affect, cognition, and activity. Thus a functional change in the DRD3 gene could in turn affect the cognitive and psychiatric symptoms of dementia of Alzheimer's type (DAT). We investigated a possible association of DRD3 genotype with DAT and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for DRD3 and apolipoprotein E (ApoE) was determined using restriction fragment length polymorphism in 210 patients with mild DAT and 224 age- and sex-matched non-demented controls. The occurrence of BPSD during the course of mild dementia was demonstrated using the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). No significant differences in DRD3 genotype were identified between DAT and controls, regardless of ApoE epsilon4. Among the DAT with BPSD, however, a significant association was observed between the presence of the DRD3 glycine allele and paranoid and delusional ideation, regardless of ApoE epsilon4. In conclusion, DRD3 gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of paranoid and delusional ideation during the course of mild DAT.

IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type.

Insulin degrading enzyme (IDE) degrades amyloid beta (Abeta), which may inhibit the accumulation of Abeta in a brain affected with dementia of Alzheimer's type (DAT). A decrease in the activity of IDE results in changes in glucose utilization in the brain, which could affect the cognitive and psychiatric symptoms of DAT. We investigated a possible association of IDE gene polymorphism and the behavioral and psychological symptoms of dementia (BPSD) in mild DAT. The genotyping for IDE and apolipoprotein E (ApoE) was determined in 207 patients with mild DAT and 215 controls. The occurrence of BPSD was demonstrated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). IDE gene polymorphism is unlikely to play a substantial role in conferring susceptibility to DAT, but it may be involved in the development of affective disturbance through the course of mild DAT, regardless of the presence of an ApoE epsilon4 allele. The present data could be the result of a small sample size. Further investigations using larger samples are thus required to clarify the correlation between IDE gene polymorphism, susceptibility to DAT, and emergence of BPSD.

Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type.

Amnestic mild cognitive impairment (MCI) describes the condition of memory-impaired individuals who otherwise function well and do not meet the clinical criteria for dementia. Such individuals are considered to represent a transitional stage between normal aging and dementia of Alzheimer type (DAT). Neurobiologic changes in amnestic MCI, and their significance for psychophysiologic function, are poorly understood. In this study, the authors compared acoustic prepulse inhibition (PPI) between subjects with amnestic MCI and mild DAT to characterize sensorimotor gating. The acoustic startle reflex, which the authors measured using an accelerometer and electromyogram, involves whole-body movement and eye blink in response to a sudden loud noise (115 dB). PPI is inhibition of this reflex by a softer noise (prepulse; 85 dB) preceding the startle stimulus by 30 ms. PPI was examined in 30 controls, 20 subjects with amnestic MCI, and 20 subjects with mild DAT. Neither amnestic MCI nor mild DAT affected startle movement amplitude. Subjects with amnestic MCI showed significantly enhanced PPI (gating facilitation), while subjects with mild DAT exhibited significantly less PPI than controls (gating deficit). This pattern of PPI changes suggests that neuropathologic changes in the limbic cortex, mainly the entorhinal cortex, at the earliest stage of DAT might be responsible for PPI abnormalities via disturbed regulation of the limbic cortico-striato-pallido-pontine circuitry. Startle PPI changes could be used as a biologic marker for amnestic MCI and mild DAT.

Involvement of nucleus accumbens dopaminergic transmission in acoustic startle: observations concerning prepulse inhibition in rats with entorhinal cortex lesions.

The relationship between the entorhinal cortex and prepulse inhibition (PPI) as well as the nucleus accumbens dopaminergic participation in acoustic startle were examined in rats. After the entorhinal cortex was damaged bilaterally using ibotenic acid, a microdialysis probe was placed in the nucleus accumbens for detection of dopamine before, during and after acoustic startle stimuli. In rats with bilateral entorhinal cortex lesions PPI was reduced, and extracellular dopamine in the nucleus accumbens was elevated with or without acoustic stimuli. The entorhinal cortex and the sensorimotor gating system thus may be related via dopaminergic connections in the nucleus accumbens, even though dopamine release did not coincide completely with acoustic startle stimuli.