Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

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 Alzheimer's 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 Alzheimer's 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.

Endogenous estradiol in elderly individuals: cognitive and noncognitive associations.

OBJECTIVE: To investigate an association between endogenous estradiol (E(2)) levels and cognition and behavior in elderly individuals. PATIENTS: We studied 135 community-based men and women aged 52 to 85 years in urban Bangkok, Thailand; 72 had dementia and 63 did not. MATERIALS AND METHODS: Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria after appropriate investigations. Blood samples for assay were collected in the morning after 6 hours of fasting. Levels of E(2) were measured by radioimmunoassay (double antibody technique). The Thai version of the Mini-Mental State Examination was used to assess cognition; the Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms; and the Functional Assessment Questionnaire was used to assess instrumental activities of daily living. RESULTS: There was no correlation between age and level of E(2) in either men or women. Individuals with lower estrogen levels had more behavioral disturbances (men: r = -0.467, n = 45; P =.001; women: r = -0.384, n = 90; P<.001) and worse cognition (men: r = 0.316, n = 45; P =.03; women: r = 0.243, n = 90; P =.02) and function (men: r = -0.417, n = 45; P =.004; women: r = -0.437, n = 90; P<.001). The threshold level of endogenous E(2) in elderly individuals for the risk of developing dementia was less than 15 pg/mL (<55 pmol/L) in men and less than 1 pg/mL (<4 pmol/L) in women. CONCLUSION: Lower E(2) levels are correlated with poor cognitive, behavioral, and functional status in older individuals.

Surface electromyography in patients with tension-type headache and normal healthy subjects.

Headache is one of the most common medical symptoms and tension - type headache is the most common form. Pericranial muscles have been invoked as a source of nociception among patients with tension - type headache. This study was performed to determine surface electromyography (EMG) as representative of the electrical activity of pericranial muscles in tension - type headache and normal subjects during rest and mental calculation. Surface EMG recordings were performed in 20 normal subjects (age 33.9 +/- 8.9 years) and 20 tension-type headache patients (34.5 +/- 9.4 years) using electroencephalograph during the initial rest period for 5 minutes, during mental calculation for 2 minutes and 3 minutes of the rest period. Surface EMG was scored as discharge score (DS) at the third, sixth and ninth minute. The DS at each minute studied showed that the headache group had higher electrical activity than the normal group and increased EMG activity during mental stress was found in the headache group.

Epidemiology of stroke in the elderly in Thailand.

Epidemiology of stroke in the elderly in Thailand was conducted from August 1994 to October 1996. The total of 3,036 Thai elderly were included in this study. They represented the elderly population from four regions; Central Region (615 elderly, Nakhon Pathom Province), Northern Region (840 elderly, Lampang Province), North-Eastern Region (706 elderly, Sakon Nakhon Province), and Southern Region (857 elderly, Ranong Province). All elderly in these selected areas received general physical examinations and complete neurological examinations from neurologists. Demographic data concerning each individual was recorded by specially trained nurses. Data included age, sex, occupation, education, drug usage, alcohol, smoking and pre-existing diseases. Blood was taken from each subject for complete blood count, fasting blood sugar, cholesterol, triglyceride, high density lipoprotein cholesterol and VDRL. Data on physical examinations were recorded with particular attention to blood pressure, carotid bruit, cardiac murmurs, cardiac arrhythmia, speech, posture, gait, frontal lobe releasing signs, Babinski sign and focal neurological deficit. Thirty-four stroke patients were identified from 3,036 elderly (prevalence rate of 1.12 per cent). There were 12 stroke patients from Central Region (prevalence rate of 1.99 per cent), 5 from Northern Region (0.6 per cent), 4 from North-Eastern Region (0.6 per cent) and 13 from Southern Region (1.5 per cent). Hypertension was the main risk factor for stroke in this study whereas diabetes mellitus, smoking, alcohol consumption, hyperlipidemia and underlying heart diseases were insignificant risk factors. The prevalence of hypertension in Thai elderly was ranging from 16.7 to 47.2 per cent (criteria over 140/90 mmHg) or 6.1 to 24.8 per cent (criteria over 160/90 mmHg). Prevalence of smoking and alcohol consumption in Thai elderly ranged from 19.5 per cent (Sakon Nakhon) to 62.1 (Lampang) and 16.75 per cent (Nakhon Pathom) to 33.70 per cent (Lampang) respectively. Data from physical examinations revealed that dysarthria, hemiplegic gait and Babinski sign were the significant signs for diagnosis of stroke in the community setting. The prevalence of carotid bruit, cardiac murmur and cardiac arrhythmia were ranging from 1.3 to 1.8 per cent, 3.1-7.1 per cent and 0.8-1.4 per cent respectively. From this study, it can be concluded that stroke prevention is the best policy for stroke management. Stroke prevention measures should thus be aimed at the high risk elderly group. This is best achieved by identifying risk factors among them and then controlling these risk factors properly.

The IQCODE: an alternative screening test for dementia for low educated Thai elderly.

OBJECTIVE: To explore an alternative method of screening for dementia in Thai elderly people who have a low educational level. The Informant Questionnaire on Cognitive Decline in the elderly (IQCODE) is used as the screening test. MATERIAL AND METHOD: A community based population of elderly subjects in Bangkok including 87 normal subjects and 73 demented elderly people were studied. Their ages ranged from 52 to 85 years old. The majority of the elderly people had had four years or less of primary-education. Dementia was diagnosed independently by DSM IV criteria. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), a short form, was administered to informants of the elderly by trained medical personnel. The Thai Mini Mental State Examination (TMSE) was also administered to these subjects and compared with the IQCODE. SPSS 9.0 was used for statistical analysis. RESULTS: The IQCODE showed a negative correlation with the TMSE (n=160, r=-0.679, p<0.001). The area under the receiver operating characteristic curve (ROC) of the IQCODE was larger than that of TMSE (0.928 vs 0.814). On logistic regression analysis, there were only three questions that contributed to the diagnosis that showed statistical significance. These questions are remembering what day and month it is, learning how to use a new gadget and handling other everyday arithmetic problems. Applying the new formula (z-score), these three questions showed a sensitivity of 84.90 per cent, and a specificity of 92 per cent for the diagnosis of dementia. CONCLUSION: Informants' perceptions of cognitive impairment of the elderly can be reliably applied as a screening instrument for dementia in the Thai population with a variety of educational levels. A short form of the IQCODE using selected questions can be administered with good diagnostic sensitivity and specificity.

Experience of ApoE study in Thai elderly.

UNLABELLED: The association between ApoE E4 and dementia is reported in Alzheimer's disease and other dementia such as in multi-infarct dementia. OBJECTIVES: To examine the association between apolipoprotein E genotype (ApoE) and dementia in Thai elderly and patients to examine the alleles frequencies of ApoE in a Thai population. MATERIAL AND METHOD: Seventy-eight cases and ninety-four controls from a community based population were recruited. Their ages were all over 50 years. Dementia was diagnosed by DSM IV criteria. Blood was taken and stored for DNA extraction and for restriction enzyme analysis of ApoE genotype. Descriptive analysis and odds ratios from SPSS 9.0 program were used in this study. RESULTS: Alleles frequencies of ApoE E2, E, E4 in normal controls were 0.03, 0.80, 0.17 and alleles frequencies of ApoE E3, E4 in dementia subjects were 0.71 and 0.29, respectively. Odds ratios for dementia risk of apolipoprotein genes were as follows: 0.62 for ApoE E3 and 1.98 for ApoE E4. In this study, forty-two dementia subjects had Alzheimer's disease. Fifty nine point five per cent of Alzheimer's disease subjects carried ApoE E4 (positive predictive value is 0.60). CONCLUSION: Thai elderly carry ApoE genotype distribution similar to that reported in other ethnic groups. Bearing ApoE E4 gene increases the risk of developing dementia. The use of ApoE genotyping can only be a diagnostic adjunct for Alzheimer's disease.

Risk factors for dementia and impaired cognitive status in Thai elderly.

OBJECTIVE: To examine the association of physical and biochemical risk factors for dementia and cognitive status in an urban population based Thai elderly. MATERIAL AND METHOD: This study was part of an integrated health research project from 1997 to 1999. Subjects were 550 elders who lived in a community within 10 km from Siriraj Hospital, Bangkok, Thailand. They were 55 years and older. Thai mental state examination (TMSE) was applied to all subjects as the screening test for dementia. Those who scored less than or equal to 24 out of 30 were categorised as having cognitive impairment or suspected of having dementia, and they were then examined in detail for the diagnosis of dementia using the DSM IV criteria. Blood pressure and body weight were recorded. Blood was drawn for biochemical and haematological analysis including the serology for syphilis and thyroid function test as the basic screening investigation for dementia. Descriptive data, expressed as the mean, standard deviation, Pearson Chi square and ANOVA tests were analysed with SPSS 9.0 in the study. RESULTS: Of 550 subjects, 261 (47.45%) were classified as the normal subjects group, 49 (8.91%) as the cognitively impaired group, and 240 (43.82%) as the dementia group. 377 subjects (68.55%) were female and the distribution of females in each subgroup ranged from 63.3-75.5 per cent. The mean age in the normal group was 67.47 +/- 6.05 years, the cognitively impaired group was 70.14 years and the dementia group was 69.63 +/- 9.21 years. Systolic blood pressure (BP), diastolic BP, serum cholesterol, SGOT, GGT, serum albumin, haemoglobin, MCHC, neutrophil counts and weight were statistically significant factors that were associated with cognitive status. Both systolic and diastolic BP were high in the higher cognitive status group. Serum albumin, serum cholesterol levels and body weight were also higher in the high cognitive status group. CONCLUSION: This study demonstrated an association between nutritional status and cognitive status in Thai elderly. Poorer nutritional factor in lower cognitive function individuals might explain a lower of both systolic and diastolic BP in the dementia subjects compared to the healthy subjects.

Cognitive status in the community dwelling Thai elderly.

OBJECTIVE: To survey the prevalence of cognitive impairment in the elderly and to estimate the prevalence of dementia in the community dwelling Thai population. To assess the psychometric property of Thai Mental State Examination (TMSE). MATERIAL AND METHOD: We conducted a countrywide survey of 3,177 Thai elderly who were 60 years old and over from 1995 to 1997. Medical history and ability to carry out daily activities were taken by trained medical personnel. Thai Mental State Examination (TMSE) was used for cognitive study. Every elderly person involved in this study was examined by either an internist or a neurologist. Blood was taken for haematological and biochemical analysis. SPSS 6.0 was the main statistical analysis of the data. RESULTS: Three thousand one hundred and seventy seven elderly people were enrolled in this study, thirty eight point eight per cent were male and sixty one point two per cent were female. There was correlation between age, education and TMSE (r=-0.345, r=0.473, p<0.001). We found no correlation between TMSE, mean arterial blood pressure (BP), systolic BP, diastolic BP, haematocrit, cholesterol, triglyceride, blood sugar and syphilitic serology. Multiple cut off points of TMSE was proposed to utilise the twenty fifth percentile in each five yearly age interval. Those who were under the 25th percentile of TMSE and had impaired daily activities were diagnosed as dementia. The prevalence of dementia was 9.88 percentiles in our study. CONCLUSION: Dementia is a common problem in the Thai elderly. As treatment has become available for several etiologies of dementia, early detection and assessment of dementia with a cognitive screening test are essential. Public education to distinguish between dementia and old age needs to be emphasised.

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 (Aß 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. Aß 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 Aß 1-42, tTau, ptau (181), and pTau/Aß 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 Aß 1-42, tTau, pTau (181), and pTau/Aß 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 Aß 1-42, tTau, pTau (181), and pTau/Aß 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 Aß 1-42 and pTau/Aß 1-42. We propose mean + 1.5 SD of CSF Aß 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 Aß 1-42 and CSF p-tau/Aß 1-42 among those with AD, non-AD dementia and non cases with SMC without dementia in Thai cohort. Cut-off point of CSF Aß 1-42 of 331.57 pg/mL is suggested in Thai study.

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 Alzheimer's disease (AD) patients with or without cerebrovascular disease and vascular dementia (VaD). A 6-month, multicentre, open-label, uncontrolled trial was undertaken in 75 AD patients. Eligible patients received an initial galantamine dose of 8 mg/day and escalated over 5-8 weeks to maintenance doses of 16 or 24 mg/day. Primary efficacy measures were AD Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change-Plus version (CIBIC-plus). The Behavioural Pathology in AD Rating Scale (BEHAVE AD), the AD Cooperative Study Activities of Daily Living Inventory and Pittsburgh Sleep Quality Index were the secondary efficacy variables. Analyses were based on the intent-to-treat population. Treatment with galantamine showed significant improvement in cognition on the ADAS-cog and CIBIC-plus at month 6. Galantamine showed favourable effects on activities of daily living. Behavioural symptoms and sleep quality were also significantly improved (p < 0.05). Galantamine was well tolerated. The adverse events were mild-to-moderate intensity. The most frequent adverse events commonly reported were nausea (16.4%), dizziness (9.6%) and vomiting (6.8%). The results of this study may be consistent with galantamine being an effective and safe treatment for mild-to-moderate AD patients with or without cerebrovascular disease and VaD. Flexible dose escalation of galantamine was well tolerated. The daily maintenance dose of galantamine was 16 mg/day, followed by a back up dose of 24 mg/day.

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.