Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia

Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer’s Disease Patients in Asia

Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Clinical Aspects of Neurobehavioral Symptoms of Dementia

Neurobehavioral symptoms of dementia (NBSD) are very common and are significant symptoms of the illness, contributing most to caregiver burdens and often resulting in premature institutionalization of the person with dementia. The main symptoms of NBSD are anxiety, depression, delusions, and hallucinations. NBSD produce significant problems for both patients and caregivers. The pathophysiology of NBSD is determined by genetic, structural, or environmental factors. Therefore, treatment of NBSD requires continuous and organic cooperation between patients, caregivers, social environments, and doctors. Therefore, it is important for neurologists, who mainly view NBSD for dementia patients, to increase their understanding of these more comprehensive areas as well as the latest insights and treatments to help patients and caregivers.

Role of cerebrovascular risk factors in dementia

With the rapid increase in the prevalence of dementia worldwide there has been significant research into modifiable risk factors for dementia. In this regard cerebrovascular diseases (CVD) represent a potential therapeutic target in the fight against the epidemic of dementia. Both large vessel CVD and small vessel disease in the form of chronic lacunes, white matter hyperintensity, microbleeds, and perivascular spaces have been strongly associated with the risk of developing dementia. These CVD factors may initiate or accelerate the amyloid and tau cascades resulting in greater rates of neurodegeneration and dementia. Understanding the precise mechanisms for the interaction between CVD and neurodegeneration will allow development of potential interventional targets. These CVD risk factors may be of particular relevance to the Asian population where a high burden of small vessel CVD has been demonstrated in Asian patients with dementia

Psychometric Properties of Alzheimer's Disease Assessment Scale-Cognitive Subscale for Mild Cognitive Impairment and Mild Alzheimer's Disease Patients in an Asian Context

<p><b>INTRODUCTION</b>The purpose of the current study is to assess the psychometric properties of Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) on patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) in a multicultural Asian context.</p><p><b>MATERIALS AND METHODS</b>Sixty-four mild AD patients (mean age ± SD; 72.24 ± 7.88 years), 80 MCI patients (66.44 ± 7.45 years) and 125 healthy controls (HCs) (61.81 ± 6.96 years) participated in the study. Participants underwent a clinical interview and serial neuropsychological testing. ADAS-Cog total and subtest scores were compared across the 3 groups. Receiver operating characteristics (ROC) analysis were performed and sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated.</p><p><b>RESULTS</b>Patients with MCI attained significantly worse neuropsychological test scores than healthy controls but significantly better results than patients with mild AD on ADAS-Cog total score, subtest items, and the delayed recall item (P <0.001). The best cutoff score to differentiate between MCI and HC was ≥4 (sensitivity = 0.73, specificity = 0.69, PPV = 0.90, NPV = 0.40), while the best cutoff score to distinguish between MCI and mild AD was ≥12 (sensitivity = 0.86, specificity = 0.89, PPV = 0.99, NPV = 0.32). Evidence of internal consistency of the ADAS-Cog (Cronbach α = 0.85) as well as convergent validity with the Mini-Mental State Examination (MMSE) (ρ = -0.75) and Montreal Cognitive Assessment (MoCA) (ρ = -0.81) (both P <0.001) was also found.</p><p><b>CONCLUSION</b>The ADAS-Cog which is widely used in clinical trials is applicable to the Asian cohort. It is useful in the detection of MCI and mild AD as well as in distinguishing these 2 conditions.</p>

Association Analysis of COQ2 Variant in Dementia and Essential Tremor.

Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions. Materials & Methods. A total of 2064 subjects, including 560 patients with dementia, 466 patients with ET, and 1038 healthy controls, were included. Genotyping for the COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender, together with 95% confidence interval (CI), was reported by means of logistic regression. Results. The frequency of the polymorphic variant V393A heterozygous (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95% confidence interval is 0.29-1.72 for dementia, and OR = 0.47, 95% confidence interval is 0.17-1.31, p = 0.1217 for ET). There was no significant association between V393A variant with dementia and ET. Conclusion. There was no significant association between V393A variant with dementia and ET. COQ2 gene is unlikely to play a significant role in patients with dementia or ET in our population.

Overview of Dementia and Diagnosis of Dementia

Dementia is a syndrome characterised by cognitive, behavioural and neurological deficits. Both neurodegenerative and non-neurodegenerative conditions can result in dementia. Neurodegenerative diseases include diseases such as Alzheimer’s disease, Frontotemporal Dementia and Dementia with Lewy body, while nonneurodegenerative conditions include conditions such as vascular dementia and normal pressure hydrocephalus. The prevalence of dementia is on a rising trend with the rapidly ageing population in Singapore. Early diagnosis of dementia is important to allow timely pharmacological and non-pharmacological interventions. A thorough history, cognitive evaluation along with suitable investigational studies is necessary for early diagnosis. The ability to diagnose dementia at the earliest stages has been greatly improved with the use of biomarkers such as medial temporal atrophy on MR imaging and cerebrospinal fluid beta amyloid levels. A 4-step approach to dementia evaluation, incorporating local data, where possible can be used: The first step requires the exclusion of delirium as the cause of the forgetfulness or confusion; the second step involves establishing the diagnosis of dementia; the third step assesses for the behavioural, functional and social problems associated with dementia; and the final step, with the use of a focused history, physical examination, investigations and selected use of neuroimaging, attempts to establish the aetiological diagnosis of the dementia. The management of dementia requires a multidisciplinary approach. While acetyl cholinesterase inhibitors and NMDA antagonist can slow cognitive deterioration, research for newer disease modifying drugs which target the underlying pathology is ongoing. Research into nonpharmacological interventions such as cognitive training is also on-going.

Effectiveness of Montreal Cognitive Assessment for the diagnosis of mild cognitive impairment and mild Alzheimer's disease in Singapore

<p><b>INTRODUCTION</b>Mild cognitive impairment (MCI) is an important clinical entity with significant management implications. However, traditional screening tools lack the sensitivity needed to detect amnestic MCI (MCI-A). Montreal Cognitive Assessment (MoCA) has yet to be validated for the diagnosis of MCI in a multiracial society such as Singapore. We thus aimed to study the effectiveness of MoCA for the diagnosis of MCI-A in the Singapore population.</p><p><b>METHODS</b>Data on patients with MCI-A and mild Alzheimer's disease (AD) was obtained from a prospectively collected clinical database between January 2008 and January 2011. Patients with no cognitive impairment (NCI) were recruited from among the spouses and friends of patients attending the memory clinic.</p><p><b>RESULTS</b>There were a total of 212 participants (103 NCI, 49 MCI-A, 60 mild AD). For the diagnosis of MCI-A, a MoCA score of < 26 for patients with ≤ 10 years of education, and a score of < 27 for patients with > 10 years of education provided a sensitivity of > 94%. For the diagnosis of mild AD, a MoCA score of < 24 for patients with ≤ 10 years of education, and a score of < 25 for patients with > 10 years of education provided a sensitivity of > 85%.</p><p><b>CONCLUSION</b>In the Singapore population, we recommend cutoff scores of 26/27 and 24/25 be used to detect MCI-A and mild AD, respectively, when using MoCA. For patients with ≤ 10 years of education, a +1 point correction is needed.</p>