Vorapun Senanarong

Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.

Objectives: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer’s disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. Methods: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer’s Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. Results: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. Conclusion: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.

Neuropsychiatric symptoms, functional impairment and executive ability in Thai patients with Alzheimer's disease

BACKGROUND Instrumental activities of daily living (IADL) depend on executive planning and procedural memory mediated by the frontal lobes. Planning and judgment are involved in clock drawing. Neuropsychiatric symptoms are also mediated by frontal lobes, and a relationship between ADL, clock drawing and neuropsychiatric symptoms was hypothesized. OBJECTIVE To investigate the relationship between behavioral disturbances, ADL, and executive function. METHODS Seventy-three Thai patients with Alzheimers disease (AD) were evaluated. Neuropsychiatric symptoms and behaviors were assessed with the Nevropsychiatric Inventory (NPI). The Thai version of the Mini-mental State Examination (TMSE) was utilized as a global cognitive assessment. A clock-drawing test (CDT) and both category (animals) and letter (ko, so in Thai) verbal fluency were used as executive measures. Thai ADL scale, Barthel Index (BI), and Functional Assessment Questionnaire (FAQ) were ADL measures used in this study. RESULTS There were statistically significant correlations between CDT and the frontally-mediated behaviors of agitation (r = -0.367), apathy (r = -0.273) and disinhibition (r = -0.247). Verbal fluency correlated with agitation (r = -0.341). There were significant correlations between Thai ADL scores and agitation (r = 0.350), apathy (r = 0.441), and disinhibition (r = 0.417). FAQ correlated with the same three behaviors. After controlling for TMSE, a significant correlation remained between Thai ADL scores and agitation (r = 0.291) and apathy (r = 0.342). CONCLUSIONS We demonstrated correlations between ADL and behavioral changes in Thai elderly with AD. Our results emphasize the important relationships among behavioral changes and impaired ADL.

A New Measurement of Activities of Daily Living for Thai Elderly with Dementia

BACKGROUND Activities of daily living (ADL) vary across cultures, and measure of ADL needs to be specific to the population under study. We developed an ADL measure for Thai elderly with dementia and investigated the reliability and validity of this instrument. MATERIALS AND METHODS Item construction was accomplished with a panel of neurologists and a rehabilitation medicine physician. One hundred eighty-one subjects were interviewed using the Thai ADL measure. Of this sample, one hundred fifty-nine had dementia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. These data were analyzed for internal consistency; concurrent validity was determined by comparison with the Barthel Index, Functional Assessment Questionnaire (FAQ), Thai Mental State Exam (TMSE), and Clinical Dementia Rating (CDR) scale; and discriminant validity was determined by comparison with the Neuropsychiatric Inventory (NPI). Thirty subjects were tested to determine interrater and test-retest reliability. RESULTS Thai ADL measure was composed of six basic ADL and seven instrumental ADL. It had high correlation with TMSE scores (r = -.69), CDR scores (r = .81), Barthel Index scores (r = -.80), and FAQ scores (r = .88), and moderate correlation with NPI scores (r = .46). The instrument had high test-retest reliability (intraclass correlation coefficient [ICC] = .92, .89) and high interrater reliability (ICC = .96, .93). CONCLUSION The Thai ADL scale is easy to use and it has high reliability. It had high concurrent validity with previously published ADL scales. The methodology used to develop the Thai ADL scale can provide a model for creating culturally competent ADL scales.

Efficacy study of galantamine in possible Alzheimer's disease with or without cerebrovascular disease and vascular dementia in Thai patients: a slow-titration regimen.

The objective is to evaluate the efficacy of galantamine when a slow titration regimen is employed in Thai Alzheimers disease (AD) patients with or without cerebrovascular disease and vascular dementia (VaD).

Intellectual and physical activities, but not social activities, are associated with better global cognition: a multi-site evaluation of the cognition and lifestyle activity study for seniors in Asia (CLASSA)

BACKGROUND population ageing will lead to a leap in the dementia population in Asia. However, information about potentials for low-cost and low-risk interventions is limited. OBJECTIVES to study the associations between lifestyle activities and global cognition from the Cognitive and Lifestyle Activity Study for Seniors in Asia (CLASSA). DESIGN a cross-sectional study. METHODOLOGY we studied the association between global cognition and lifestyle activity participation in community living older adults (60 years or over) across nine sites in East Asia. A standardised lifestyle activity questionnaire exploring activities from four categories (intellectual, physical, social and recreational) was used to measure the pattern. Global cognition was categorised by locally validated versions of Mini-mental state examination (MMSE) or Montreal Cognitive Assessment (MoCA) (good cognition, GC-scored at the top 25% among participants with no significant cognitive deficit (SCD); normal cognition, NC-middle 50% among participants with no SCD; mild cognitive deficit, MCD-lowest 25% among participants with no SCD; SCD-below local cut-offs for dementia). RESULTS two thousand four hundred and four (1,009 men; 1,395 women) participants were recruited. The mean age was 71.0 (7.2) years. A higher variety of intellectual and physical activities were associated with GC; more social activities were associated with higher risks of having impaired cognition (multinomial logistic regression). The same association was found in participants with no SCD and had regular activities for over 10 years (n = 574). CONCLUSION intellectual activity and physical exercise were associated with better cognitive states in Asian older adults. Community-based intervention may take considerations into specific types of activities to optimise cognition.

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.

Galantamine for the treatment of BPSD in Thai patients with possible Alzheimer's disease with or without cerebrovascular disease.

Objectives. This study was to investigate an efficacy of galantamine in treatment of behavioral and psychological symptoms of dementia in Thai elderly who suffered from possible Alzheimers disease (AD) with or without cerebrovascular disease and vascular dementia. Methods. A 6-month, multicenter, open-label, uncontrolled trial was undertaken in 75 patients. Eligible patients received an initial galantamine dose of 8 mg/dayand escalated over 5 to 8 weeks to maintenance doses of 16 or 24 mg/day. The behavioral response was assessed as an intention-to-treat analysis using the Behavioral Pathology in Alzheimers Disease Rating Scale (BEHAVE-AD). Results. Galantamine improved behavioral and psychological symptoms of dementia (P < .05 vs baseline) over the 24 weeks of treatment. BEHAVE-AD score was significantly improved from baseline in paranoid and delusion ideation, diurnal rhythm disturbances, anxieties, and phobias. Conclusions. Galantamine may be a well-tolerated and effective treatment option for improving psychotic, behavioral, and psychological symptoms in Thai elderly with possible AD with or without cerebrovascular disease and vascular dementia.

The platelet amyloid precursor protein ratio as a diagnostic marker for Alzheimer’s disease in Thai patients

The platelet amyloid precursor protein (APP) ratio has recently been shown to be a promising diagnostic marker for Alzheimers disease (AD). To evaluate its usefulness in Thai patients, platelet APP was analyzed by immunoblotting. The APP ratio was calculated as the ratio of the combined band density of the 120-kD and 130-kD isoforms compared to that of the 110-kD isoform. The mean ages (and ranges) of 27 normal and 13 AD-affected subjects were 68.3 (60-84) and 79.3 (70-97) years, respectively. The Thai Mental State Examination (TMSE) scores demonstrated that the AD patients had significantly poorer cognitive functions than the normal subjects, with mean TMSE scores of 20.3 and 27.6 (maximum score of 30 points), respectively (p<0.05). The platelet APP ratios of the AD patients were significantly lower than those of normal subjects: values (mean ± standard deviation) were 7.32 ± 1.29 and 9.13 ± 3.00, respectively (p<0.05) for AD patients and normal subjects. However, the ranges of the APP ratios from both groups markedly overlapped, which precluded the establishment of a cutoff level to differentiate between the AD and normal subjects. In addition, no significant correlations were observed between the platelet APP ratio and the TMSE score or between the APP ratio and the serum cholesterol in this study, in contrast to previous reports.

Priorities for research consortia on Alzheimer's disease.

Coordination and harmonization of efforts between five major research consortia on Alzheimers disease may increase our understanding of this condition and improve our therapeutic approaches. Specific opportunities include a registry for families with early onset dementia, a study registry, minimal data sets, validation of assessment tools and outcomes, update on ethical issues, resolution of methodological issues, new investigators training, longitudinal observation studies, prevention studies, and liaison with stakeholders such as Alzheimer Disease International.

Alzheimer’s Disease Dementia as the Diagnosis Best Supported by the Cerebrospinal Fluid Biomarkers: Difference in Cut-Off Levels from Thai Experience

Objectives. To determine how beta-amyloid 1-42 (Aβ 1-42), total tau (tTau), and phosphorylated tau (pTau) levels in CSF behave in a cohort of Thai patients from the Memory Clinic in Bangkok, Thailand. Methods. During 2009–2011, twenty eight subjects from the memory clinic at Siriraj Hospital had CSF analysis for AD biomarkers. Aβ 1-42, tTau, and pTau (at amino acid 181) were measured in CSF by ELISA technique. Results. Mean of Thai mental state examination (TMSE) of 28 Thai cohort was 16.48 (6.63). Fourteen had AD, ten had non-AD dementia, and four non-cases were those with subjective memory complaint (SMC) without dementia. Mean CSF Aβ 1-42, tTau, ptau (181), and pTau/Aβ 1-42 in the AD group were 241.36 (60.14) pg/mL, 222.79 (212.24) pg/mL, 40.79 (27.84) pg/mL, and 0.18 (0.12) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-AD dementia group were 430.40 (125.18) pg/mL, 349.30 (692.16) pg/mL, 36.80 (14.90) pg/mL, and 0.09 (0.04) accordingly. Mean CSF Aβ 1-42, tTau, pTau (181), and pTau/Aβ 1-42 in the non-cases with SMC without dementia were 499.75 (93.44) pg/mL, 137.25 (62.74) pg/mL, 31.75 (17.48) pg/mL, and 0.06 (0.02). There is significant difference (P < 0.05) among the 3 groups in CSF Aβ 1-42 and pTau/Aβ 1-42. We propose mean + 1.5 SD of CSF Aβ 1-42 in AD group (331.57 pg/mL) to be the cut-off point in Thai subjects. Conclusion. There are significant different in CSF Aβ 1-42 and CSF p-tau/Aβ 1-42 among those with AD, non-AD dementia and non cases with SMC without dementia in Thai cohort. Cut-off point of CSF Aβ 1-42 of 331.57 pg/mL is suggested in Thai study.