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Background/Aim:To investigate the predictive ability of the previously established global cerebrovascular disease (CeVD) burden scale on long-term clinical outcomes in a longitudinal study of Asian elderly participants across the spectrum of cognitive impairment.Methods:A case-control study was conducted over a 2-year period involving participants with no cognitive impairment, cognitive impairment-no dementia (CIND), and Alzheimer's disease (AD). Annually, cognitive function was assessed with a comprehensive neuropsychological battery and the clinical dementia rating (CDR) scale was used to stage disease severity.Results:Of 314 participants, 102 had none/very mild CeVD, 31 mild CeVD, 94 moderate CeVD, and 87 severe CeVD at baseline. There was a 1.14 and 1.42 units decline per year on global cognitive z-scores in moderate and severe CeVD groups, respectively, compared to none/very mild CeVD. Moderate-severe CeVD predicted significant functional deterioration at year 2 (HR = 2.0, 95% CI = 1.2–3.4), and conversion to AD (HR = 6.3, 95% CI = 1.7–22.5), independent of medial temporal atrophy.Conclusion:The global CeVD burden scale predicts poor long-term clinical outcome independent of neurodegenerative markers. Furthermore, CeVD severity affects the rate of cognitive and functional deterioration. Hence, cerebrovascular burden, which is potentially preventable, is a strong prognostic indicator, both at preclinical and clinical stages of AD, independent of neurodegenerative processes.

Case finding for cognitive impairment (CI) is recommended for all persons older than 70 years.The present study identified additional risk factors of CI so as to operationalize a composite total risk score (TRS) for case finding. We then examined the additive effect of the TRS and brief cognitive tests to improve the diagnosis of CI.The study was conducted in 2 primary health care centers in Singapore. A total of 1082 individuals (≥60 years old) were assessed for sociodemographic risk factors and their informants were administered the AD8; 309 individuals who agreed for further cognitive assessments completed the Mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA), and a neuropsychological battery at a research center. Primary health care medical records were accessed for data on vascular risk factors.Of the 309 individuals who underwent neuropsychological evaluation, 4 were excluded due to missing medical data; 167 (54.8%) individuals had CI and 138 (45.2%) had No Cognitive Impairment (NCI). The β coefficients were standardized to calculate risk scores. CI was significantly predicted by age70 years (odds ratio [OR] 5.99; score = 3), diabetes (OR 3.36; score = 2), stroke (OR 2.70; score = 1), female gender (OR 2.02; score = 1) and individual cognitive complaints (SCC) (OR 1.95; score = 1). The TRS had an optimal cutoff of ≥3 and explained considerable variance in global cognitive composite Z-scores (R(2) = 0.41, P .001). The MoCA explained substantial variance compared with the MMSE and AD8 (R(2) changes of 0.474, 0.422, and 0.157, P .001, respectively).The TRS is a reasonable measure to predict individuals at risk of CI. The addition of the MoCA, in persons with positive TRS scores, is a useful approach to improve the diagnosis of CI for at-risk patients attending primary health care.

Objectives:To investigate the presence of neuropsychiatric symptoms (NPS) and sub-syndromes in elderly community-dwelling Asians with varying severity of cognitive impairment.Methods:Chinese and Malay participants (n = 613) from the Epidemiology of Dementia in Singapore (EDIS) Study aged ≥ 60 years underwent clinical examination, neuropsychological testing, and NPS assessment using the Neuropsychiatric Inventory (NPI). Diagnosis of no cognitive impairment (NCI), cognitive impairment-no dementia (CIND), including CIND-mild and CIND-moderate, and dementia were made using established criteria.Results:A significant increase in the numbers of NPS was observed accompanying with increasing severity of cognitive impairment (p < 0.001). Compared to those with NCI/CIND-mild, participants with CIND-moderate [Odds ratio (OR): 4.2, 95% confidence interval (CI): 1.8–10.0] or dementia [OR: 9.2, 95% CI: 2.3–36.0] were more likely to have two or more neuropsychiatric sub-syndromes. Participants with CIND-moderate were more likely to have hyperactivity [OR: 2.0, 95% CI: 1.0–3.8] and apathy [OR: 2.9, 95% CI: 1.0–8.4] sub-syndromes, whereas patients with dementia were more likely to have psychosis [OR: 6.9, 95% CI: 2.4–20.1], affective (OR: 8.7, 95% CI: 1.8–42.9), and hyperactivity (OR: 5.4, 95% CI: 1.8–16.1). Furthermore, executive dysfunction and visual memory impairment were associated with the presence of three neuropsychiatric sub-syndromes; whist language and visuomotor speed impairment were related to the presence of two sub-syndromes. By contrast, impairment in attention, verbal memory, and visuoconstruction were not associated with any of the sub-syndromes.Conclusions:The presence of NPS and sub-syndromes increase with increasing severities of cognitive impairment, and different neuropsychiatric syndromes are associated with specific impairment on cognitive domains in community-dwelling Asian elderly.

Background A total cerebrovascular disease (CeVD) burden scale was previously constructed and an inverse association of CeVD burden and cognition was found. However, the generalizability of the CeVD scale has not been examined. Objective The objective was to validate the previously constructed total CeVD burden scale by establishing its association with cognitive function and dementia diagnosis in a community sample. Methods Eligible participants were assessed on an extensive neuropsychological battery and underwent MRI scans. The total CeVD scale, comprising markers of both small- and large-vessel diseases, was derived according to previously described criteria. Association of total CeVD burden with global and domain-based cognitive performance and dementia diagnostic utility of the scale was established. Results A total of 863 participants were included in the analysis. A stepwise association of CeVD burden score with global and domain-specific cognitive function was found. Per score increase on the total CeVD burden scale was associated with 3.6 (95% CI = 2.1-6.4) times higher odds of dementia compared to dementia-free. Discussion The total CeVD burden scale is associated with cognition and dementia in a community sample. Longitudinal studies are required to establish the predictive ability of this scale.

Background Use of a total risk score (TRS) based on vascular and sociodemographic risk factors has been recommended to identify patients at risk of cognitive impairment. Moreover, combining screening tests has been reported to improve positive predictive values (PPV) for case finding of cognitive impairment. Objective We investigated the utility of the conjunctive combination of the informant-based AD8 and the performance-based National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol for the detection of cognitive impairment, defined by a clinical dementia rating (CDR) score ≥0.5, in patients at risk of cognitive impairment (TRS ≥3). Methods Participants were recruited from 2 primary healthcare centers in Singapore and received the AD8, Montreal Cognitive Assessment, Mini-Mental State Examination, CDR, and a formal neuropsychological test battery. The scores for NINDS-CSN 5-minute protocol were extracted from the Montreal Cognitive Assessment items. Area under the receiver operating characteristics curve analyses were conducted to determine the discriminant indices of the screening instruments, the conjunctive combination (ie, screened positive on both tests), and the compensatory combination (ie, screened positive in either of or both tests). Results A total of 309 participants were recruited of whom 78.7% (n = 243) had CDR = 0 and 21.3% (n = 66) had CDR ≥0.5. The conjunctive combination of AD8 and NINDS-CSN 5-minute protocol achieved excellent PPV and acceptable sensitivity (PPV 91.7%, sensitivity 73.3%). Conclusions The conjunctive combination of the AD8 and NINDS-CSN 5-minute protocol is brief and accurate, and hence, suitable for case finding of cognitive impairment (CDR ≥0.5) in patients screened positive on the TRS in primary healthcare centers.

Background:The validity and reliability of the informant AD8 in primary healthcare has not been established. Therefore, the present study examined the validity and reliability of the informant AD8 in government subsidized primary healthcare centers in Singapore.Methods:Eligible patients (≥60 years old) were recruited from primary healthcare centers and their informants received the AD8. Patient-informant dyads who agreed for further cognitive assessments received the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and a locally validated formal neuropsychological battery at a research center in a tertiary hospital.Results:1,082 informants completed AD8 assessment at two primary healthcare centers. Of these, 309 patients-informant dyads were further assessed, of whom 243 (78.6%) were CDR = 0; 22 (7.1%) were CDR = 0.5; and 44 (14.2%) were CDR≥1. The mean administration time of the informant AD8 was 2.3 ± 1.0 minutes. The informant AD8 demonstrated good internal consistency (Cronbach'sα= 0.85); inter-rater reliability (Intraclass Correlation Coefficient (ICC) = 0.85); and test–retest reliability (weightedκ= 0.80). Concurrent validity, as measured by the correlation between total AD8 scores and CDR global (R= 0.65,p <0.001), CDR sum of boxes (R= 0.60,p< 0.001), MMSE (R= −0.39,p< 0.001), MoCA (R= −0.41,p< 0.001), as well as the formal neuropsychological battery (R= −0.46,p <0.001), was good and consistent with previous studies. Construct validity, as measured by convergent validity (R≥ 0.4) between individual items of AD8 with CDR and neuropsychological domains was acceptable.Conclusions:The informant AD8 demonstrated good concurrent and construct validity and is a reliable measure to detect cognitive dysfunction in primary healthcare.

The informant AD8 has excellent discriminant ability for dementia case finding in tertiary healthcare settings. However, its clinical utility for dementia case finding at the forefront of dementia management, primary healthcare, is unknown. Therefore, we recruited participants from two primary healthcare centers in Singapore and measured their performance on the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and a local formal neuropsychological battery, in addition to the AD8. Logistic regression was conducted to examine the associations between demographic factors and dementia. Area under the receiver operating characteristics (ROC) curve analysis was used to establish the optimal cut-off points for dementia case finding. Of the 309 participants recruited, 243 (78.7%) had CDR = 0, 22 (7.1%) CDR = 0.5, and 44 (14.2%) CDR ≥1. Age was strongly associated with dementia, and the optimal age for dementia case finding in primary healthcare settings was ≥75 years. In this age group, the AD8 has excellent dementia case finding capability and was superior to the MMSE and equivalent to the MoCA [AD8 AUC (95% CI): 0.95 (0.91–0.99), cut-off: ≥3, sensitivity: 0.90, specificity: 0.88, PPV: 0.79 and NPV: 0.94; MMSE AUC (95% CI): 0.87 (0.79–0.94), p = 0.04; MoCA AUC (95% CI): 0.88 (0.82–0.95), p = 0.06]. In conclusion, the AD8 is well suited for dementia case finding in primary healthcare settings.