Nagaendran Kandiah

Absence of A673T amyloid-β precursor protein variant in alzheimer's disease and other neurological diseases

The rare variant A673T in the amyloid-β precursor protein (APP) gene has been shown to reduce the risk of cognitive impairment. We genotyped the variant in 8721 Asian individuals comprising 552 with Alzheimers disease and vascular dementia, 790 with Parkinsons disease, and 7379 controls. The A673T variant was absent in all of the subjects. Our finding suggests that the A673T protective variant is not relevant in our Asian population. Studies in other ethnic populations would clarify whether this variant is specific to specific races/ethnicities.

Montreal Cognitive Assessment for Screening Mild Cognitive Impairment: Variations in Test Performance and Scores by Education in Singapore

Background: The Montreal Cognitive Assessment (MoCA) was developed as a screening instrument for mild cognitive impairment (MCI). We evaluated the MoCAs test performance by educational groups among older Singaporean Chinese adults. Method: The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two independent studies (clinic-based sample and community-based sample) of MCI and normal cognition (NC) controls, using receiver operating characteristic curve analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). Results: The MoCA modestly discriminated MCI from NC in both study samples (AUC = 0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based sample. The MoCAs test performance was least satisfactory in the highest (>6 years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut-off of 27/28. Overall, the MoCAs test performance was not better than that of the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis was associated with a <1-point decrement in MoCA score (η2 = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η2 = 0.115 and η2 = 0.162, respectively). Conclusion: The MoCAs ability to discriminate MCI from NC was modest in this Chinese population, because it was far more sensitive to the effect of education than MCI diagnosis.

Real-world evaluation of compliance and preference in Alzheimer's disease treatment.

Purpose Rivastigmine transdermal patch has shown higher caregiver satisfaction and greater preference than oral formulation in patients with Alzheimer’s disease. However, there is limited literature available related to caregiver preference or treatment compliance in real-world clinical settings. To date, no such data are available from Asia and the Middle East, which account for a sizeable proportion of patients with Alzheimer’s disease. The objective of this study was to evaluate treatment preference and compliance with oral and transdermal medications in daily clinical practice in an ethnically diverse patient population from Asia and the Middle East with mild-to-moderate Alzheimer’s disease. Patients and methods RECAP (Real-world Evaluation of Compliance And Preference in the treatment of Alzheimer’s disease) was a 24-week, multicenter, prospective, noninterventional study. Two treatment cohorts were observed during the study: oral (cholinesterase inhibitors or memantine) and transdermal (rivastigmine patch). Caregiver preference, physician preference, and patient compliance were evaluated at week 24. Results A total of 978 of 1,931 enrolled patients (mean age: 72.8 years; 50.5% female) were in the transdermal cohort. For patients with exposure to both oral and transdermal monotherapy (n=330), a significant caregivers’ preference for the transdermal monotherapy was observed (82.7%; P<0.0001). Of the 89 participating physicians, 71 indicated preference for transdermal monotherapy. Patient compliance was also significantly higher for transdermal than oral monotherapy (P<0.0001). Conclusion Our study showed higher caregiver and physician preference and greater patient compliance with transdermal monotherapy in daily practice.

Cognitive Screening in Asia: Recognizing the Role of the Patient-Family Unit

Background/Aims: Cognitive screening programmes may improve awareness and help at-risk subjects receive earlier medical attention. Cognitive profiles of subjects who attend cognitive screening by personal choice (self-referred) compared to those where the referral was initiated by family members (family-referred) were compared. Methods: A cross-sectional survey of community subjects attending a cognitive screening initiative. Performance on the MMSE, Frontal Assessment Battery (FAB), Elderly Cognitive Assessment Questionnaire (ECAQ) and Even Briefer Assessment Scale for Depression was evaluated. Results: A total of 342 subjects with a mean age of 59.2 ± 9.0 years were screened. Overrepresentation of Chinese and Indian subjects and underrepresentation of Malay subjects was noted. The prevalence of cognitive impairment ranged from 7.0 to 9.6% depending on the screening instrument used. Of the 342 subjects, 267 were self-referred, while 75 subjects were family-referred. Family-referred subjects had lower MMSE (p < 0.001), lower ECAQ (p < 0.001) and lower FAB (p < 0.001) scores but were not more depressed compared to self-referred subjects (p = 0.904). Only the difference in ECAQ scores remained significant after adjustment for baseline differences in age and education. The prevalence of hypertension, diabetes mellitus and hypercholesterolaemia was not statistically different between the 2 groups. Conclusions: Family members play a crucial role in the diagnosis of cognitive impairment, especially in older subjects with fewer years of education.

Case-control analysis of leucine-rich repeat kinase 2 protective variants in Alzheimer's disease

Amyloid is the main pathological substrate of Alzheimers disease (AD) and has been described in leucine-rich repeat kinase 2 (LRRK2) carriers with Parkinsons disease. LRRK2 has been linked with amyloid precursor protein pathways in neurodegeneration. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple Parkinsons disease cohorts. We hypothesized that R1398H and N551K may be protective in AD. In a case-control study involving 1390 subjects (719 controls and 671 AD cases), R1398H was demonstrated in 16.8% of AD cases compared to 16.7% in controls (odds ratioxa0= 1.01, 95% confidence intervalxa0= 0.76-1.34, pxa0= 0.94), whereas N551K was demonstrated in 17.3% of AD cases compared to 17.2% of controls (odds ratioxa0= 1.00, 95% confidence intervalxa0= 0.76-1.32, pxa0= 0.98). Overall, these results suggest that LRRK2 R1398H or N551K variants do not appear to modulate the risk of AD.

PROGRESSION OF CEREBRAL SMALL-VESSEL DISEASE CORRELATES WITH CORTICAL THINNING AND COGNITIVE IMPAIRMENT IN PARKINSON’S DISEASE

rus, inferior parietal lobule, precuneus, middle temporal gyrus, superior parietal lobule, superior temporal gyrus, cingulated gyrus. Results:Among 82 MCI patients (male 21, female 61), 36 patients showed abnormal SPECT (A group) and 46 patients showed normal SPECT (N group). The age and MMSE were not significantly different between the groups. Progression from MCI to AD was observed for the period of 1-5 years. Among 61 patients observed for one year, 17 patients progressed from MCI to AD, including 6 patients in N group (35.3%) and 11 patients in A group (64.7%). The Logrank test demonstrated a significant difference in survival curve between the group A and N (P value1⁄40.00842; p<0.01). Conclusions: The eZIS and vbSEE analysis of SPECT imaging at the initial hospital visit in MCI patients is a useful tool for predicting the progression to AD in the near future.

HIGHER PERIPHERAL TREM2 MRNA EXPRESSION LEVELS ARE RELATED TO COGNITIVE DEFICITS AND HIPPOCAMPAL ATROPHY IN ALZHEIMER'S DISEASE AND AMNESTIC MCI

O2-06-06 HIGHER PERIPHERALTREM2 MRNA EXPRESSION LEVELS ARE RELATED TO COGNITIVE DEFICITS AND HIPPOCAMPAL ATROPHY IN ALZHEIMER’S DISEASE AND AMNESTIC MCI Yi Jayne Tan, Adeline Su Lyn Ng, Joseph K. W. Lim, Russell J. Chander, Ji Fang, Yingwei Qiu, Simon Ting, Shahul Hameed, NagaendranKandiah, Juan Zhou, Duke-NUSGraduateMedical School, Singapore, Singapore; 2 National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore; National Neuroscience Institute, Singapore, Singapore; National Neuroscience Institute (SGH campus), Singapore, Singapore; 5 Agency for Science, Technology and Research, Singapore, Singapore. Contact e-mail: jayne.tan@duke-nus.edu.sg

PREVALENCE OF FAMILY HISTORY OF DEMENTIA IN A SPECIALIST YOUNG-ONSET DEMENTIA CLINIC COHORT

Background:Young-onset dementia (YOD) is defined as dementia occurring before the age of 65. The most common causes include early-onset Alzheimer’s disease (EOAD), frontotemporal dementia (FTD) and vascular dementia (VAD). Pre-dementia syndromes like mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) are also prevalent in YOD clinics. FTD is known to have the highest rate of family history of dementia (40%), more so than EOAD or VAD. Rates of family history in MCI and SCI have been less studied. This cross-sectional study looked at the prevalence of family history of dementia according to disease subtype in a specialist YOD cohort. Methods: All subjects seen at a specialist YOD clinic at the National Neuroscience Institute, Tan Tock Seng Hospital between 2009 and October 2015 had their clinical charts retrospectively analysed. All available demographic, clinical and neuropsychological data were extracted. Diagnoses of EOAD, FTD, VAD, MCI and SCI were made in accordance with international consensus criteria. All subjects consented for their data to be utilized for research, and the study was approved by the Singhealth institutional review board. Statistical analyses (independent t-test and chi-square test) were performed using SPSS v20. Results: A total of 329 subjects were included in the study. Baseline characteristics according to disease subtype are listed in Table 1. The SCI group (n1⁄456) had the highest proportion of subjects with history of dementia in at least one first-degree relative at 30.4%, higher than the MCI (29.8%), AD (24.0%) and FTD (16.7%) groups. There were no significant demographic differences between SCI subjects with family history of dementia and those without, apart from baseline MMSE scores. SCI subjects with family history had a higher mean score of 29.161.0 vs 27.263.9. Conclusions: Up to 1/3 of SCI subjects had dementia history in a first-degree relative, the highest in our cohort. Whether this is the primary cause for anxiety related to subjective cognitive concerns, or if the neuropsychiatric symptoms are true harbingers of a pre-clinical degenerative illness remain to be determined. SCI patients with family history of dementia should be followed-up closely to monitor for progression to an MCI or AD state.

CAREGIVER PREFERENCE AND TREATMENT OUTCOMES IN PATIENTS WITH MILD-TO-MODERATE ALZHEIMER'S DISEASE TREATED WITH ORAL OR TRANSDERMAL MONOTHERAPY: ANALYSIS OF PROSPECTIVE DATA FROM THE RECAP STUDY

Figure 1. Perc end of study (W ness Set) Note: Effectiv during the stud effectiveness a consists of 89. zPatients in the ment were not test statistic to *A p-value <0 tions between OUTCOMES IN PATIENTS WITH MILD-TOMODERATE ALZHEIMER’S DISEASE TREATED WITH ORAL OR TRANSDERMAL MONOTHERAPY: ANALYSIS OF PROSPECTIVE DATA FROM THE RECAP STUDY Hany Mohamed Amin Aref, Nazem Bassil, Nagaendran Kandiah, Ming-Chyi Pai, Jae-Hong Lee, A.V. Srinivasan, Shelley di Tommaso, Ozgur Yuksel, Ain Shams University, Cairo, Egypt; Saint Georges Hospital, Beirut, Lebanon; National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore; National Cheng Kung University Hospital, Tainan, Taiwan; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India; Novartis Pharma AG, Basel, Switzerland. Contact e-mail: nagaendran_kandiah@nni.com.sg