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Data on the association between syphilis reactivity and dementia in memory clinic patients are scarce. We studied the prevalence of syphilis reactivity and investigated its association with dementia and markers of cerebrovascular disease (CeVD) and neurodegeneration. Data on age, gender, education, brain computed tomography scan findings and syphilis reactivity were obtained from patients who attended the National University Hospital memory clinics (February 2006–February 2016) and subjects from the community. Binary logistic regression models were used to investigate associations between syphilis reactivity and dementia, CeVD and neurodegeneration, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Of 1271 memory clinic patients eligible for the study, 57 (4.5%) were syphilis reactive, with the rate of syphilis reactivity higher in demented (44/745; 5.9%) compared to non-demented (13/526; 2.5%) patients ( p = 0.004) and non-demented community-based (21/872; 2.4%) subjects ( p

Background and aims Previous studies showed an independent association of low ankle-brachial index (ABI) with cognitive impairment. However, the association between low ABI and cognition in the presence of both cerebrovascular disease (CeVD) and neurodegeneration is lacking. We aimed at investigating a) the association of low ABI with markers of CeVD and cortical thickness, and b) whether the association of low ABI with cognition is influenced by these markers. Methods Data was drawn from the Epidemiology of Dementia In Singapore (EDIS) study where all participants (n = 832) underwent neuropsychological tests and 3T brain magnetic resonance imaging (MRI) to assess CeVD markers as well as cortical thicknesses. Cognitive function was expressed as a global composite z-score and domain-specific z-scores of a comprehensive neuropsychological battery. Results Multivariate analyses showed low ABI to be independently associated with intracranial stenosis [odds ratios (OR): 1.51; 95% confidence interval (CI):1.23–1.87] and lacunar infarcts [OR: 1.29; 95% CI: 1.06–1.57]. A low ABI was also independently associated with smaller cortical thickness globally [β: 0.09; 95% CI: 0.27–0.16] as well as with the limbic [β: 0.10; 95% CI: 0.03–0.17], temporal [β: 0.09; 95% CI: 0.02–0.15], parietal [β: 0.08; 95% CI: 0.02–0.15], and occipital [β: 0.09; 95% CI: 0.03–0.16] lobes. Low ABI was associated with worse performance in verbal memory [β: 0.06; 95% CI: 0.01–0.12], which became attenuated in the presence of MRI markers. Conclusions A low ABI is associated with MRI markers, and affects cognition in the presence of CeVD and neurodegeneration. Atherosclerosis should be targeted as a potentially modifiable risk factor to prevent cognitive disorders.

Cerebral microbleeds (CMBs) in the lobar and deep locations are associated with two distinct pathologies: cerebral amyloid angiopathy and hypertensive arteriopathy. However, the role of mixed-location CMBs in neurodegeneration remains unexplored. We investigated the associations between strictly lobar, strictly deep and mixed-location CMBs with markers of neurodegeneration. This study recruited 477 patients from a memory clinic who underwent 3T MRI scans. CMBs were categorized into strictly lobar, strictly deep and mixed-location. Cortical thickness, white matter volume and subcortical structural volumes were quantified using Free-Surfer. Linear regression models were performed to assess the association between CMBs and cerebral atrophy, and the mean difference (β) and 95% confidence intervals (CIs) were reported. In the regression analyses, mixed-location CMBs were associated with smaller cortical thickness of limbic region [β= -0.01; 95% CI= -0.02, -0.00, p=0.007) as well as with smaller accumbens volume [β= -0.01; 95% CI= -0.02, -0.00, p=0.004) and presubiculum region of hippocampus [β= -0.01; 95% CI= -0.02, -0.00, p=0.002). Strictly lobar CMBs were associated with smaller total white matter volume [β= -0.03; 95% CI= -0.04, -0.01, p

Background Cerebral small vessel disease (SVD) is one of the major contributors to cognitive impairment and dementia. However, data on the incidence and progression of SVD in an Asian population are lacking. Objective The present study aims to investigate the incidence, progression, associated risk factors, and clinical relevance of SVD in a memory clinic setting. Methods A prospective case-control study, where 346 patients underwent repeated brain MRI with a mean interval of 24.5 months, accessing white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs). Severity of cognitive impairment was assessed using Clinical Dementia Rating scale and change in clinical diagnosis. Data on demographics, vascular risk factors, and clinical history were collected at baseline. Results The prevalence of significant WMH (Fazekas ≥2) was 56.6% at baseline which progressed to 59.0% at follow-up. Overall prevalence of CMBs increased from 42.2% to 47.4% (9% new cases) and lacunes increased from 31.8% to 33.2% (2.1% new cases). Hypertension was associated with WMH progression (OR: 1.78, 95% CI: 1.01, 2.99) and increasing age was associated with incident CMBs (OR: 1.04, 95% CI: 1.01, 1.08). Moreover, the use of lipid-lowering medications decreased the incidence of lacunes (OR: 0.15, 95% CI: 0.04, 0.61). The major risk factor for incident SVD was baseline SVD lesion load. WMH progression was associated with increased severity of cognitive impairment (OR: 1.95, 95% CI: 1.16, 3.23). Conclusion Vascular risk factors and baseline severity of SVD lesion load were associated with progression of SVD. Furthermore, WMH progression was linked with increased severity of cognitive impairment. Future studies should be aimed to slow cognitive deterioration by preventing SVD related brain damage by targeting vascular risk factors.

Background:Cerebral microbleeds (CMBs) in the lobar and deep locations have been associated with two distinct pathologies namely cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy. However, the role of mixed-location CMBs in cerebrovascular disease and cognitive impairment remain unexplored. Objective: The present study aims to investigate the association of strictly lobar, strictly deep and mixed-location CMBs with cognitive impairment and dementia as well as functional decline. Methods: A prospective case-control study, where 520 patients underwent 3T brain MRI to assess region and lobe-specific CMBs, and other cerebrovascular diseases (CeVD) markers such as cortical infarcts, lacunes, and white matter hyperintensities. Patients were classified as no cognitive Impairment, cognitive impairment no dementia (CIND), and dementia [Alzheimer’s disease (AD) and vascular dementia (VaD)]. Severity of cognitive impairment was assessed using Clinical Dementia Rating scale. Results: Mixed-location CMBs were associated with dementia [Odds ratio (OR):1.23; 95% confidence interval (CI):1.04, 1.47]. When stratified by the presence of CeVD, mixed-location CMBs were associated with CIND [OR:1.20;95% CI:1.02, 1.42], AD [OR:1.22;95% CI:1.02, 1.46], and VaD [OR:1.33;95% CI:1.08, 1.62]. Furthermore, CMBs in frontal, parietal, and temporal regions were associated with CIND whereas those in parietal, temporal, and occipital regions were associated with AD. Mixed-location CMBs were also associated with increased severity of cognitive impairment [OR:1.02; 95% CI:1.00, 1.05]. Conclusion: Mixed-location CMBs are associated with cognitive impairment and dementia in the presence of CeVD. Furthermore mixed-location CMBs were linked with increased severity of cognitive impairment, suggesting severe parenchymal damage as well as microangiopathy to be common underlying mechanisms in the elderly.

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.

Purpose The present study investigated (a) the agreement between computerized tomography (CT) and 3 T magnetic resonance imaging (MRI) in the visual grading of medial temporal atrophy (MTA); and (b) whether MTA on CT differentiated patients with dementia from no dementia in memory clinics. Materials and methods Data were obtained from patients who underwent CT scans at the National University Hospital of Singapore, and from a subsample who subsequently underwent 3 T MRI scans in a research study. Agreements and disagreements between CT and MRI were determined. Area under the curve (AUC) analyses determined if CT-graded MTA distinguished patients with dementia from no dementia. Results Of the 107 patients in the subsample, MTA scores of 71 agreed on both CT and MRI. The true positive rate between CT and MRI for MTA scores ≥2 was 79.7%. The true negative rate for MTA scores between 0 and 1 was 96.4%. CT underestimated MTA severity in 33 of 36 disagreements with the MRI. MTA scores ≥2 on CT distinguished dementia from no dementia in both discovery [n=263; AUC (95% confidence interval)=0.77 (0.72-0.83); sensitivity=0.69; specificity=0.74] and validation [n=264; AUC (95% confidence interval)=0.77 (0.71-0.82); sensitivity=0.72; specificity=0.72] groups. Conclusions MTA graded on CT is a viable alternative to MRI to aid in the diagnosis of dementia in memory clinics.

Background:Despite recent interest in community-based screening programs to detect undiagnosed cognitive disorder, little is known about whether screening leads to further diagnostic evaluation, or the effects of such programs in terms of actual changes in patient or caregiver behavior. This study followed up informants of older adults (i.e. caregivers of patients who completed informant-based screening regarding the patient) following participation in a study screening for undiagnosed memory problems, to explore uptake of further diagnostic evaluation or treatment, advance planning or preparations, lifestyle changes, medication adherence, and use of support services.Methods:A total of 140 informants of older adult patients were surveyed four to fifteen months following participation in a cognitive screening study. The informants were interviewed with a study-specific survey about cognitive assessment, advance planning, lifestyle changes, and use of support services and general medication adherence.Results:A minority of patients and informants had engaged in advance planning or made relevant lifestyle changes following cognitive screening. Those assessed as being at higher risk of memory problems were more likely to have attended a full diagnostic evaluation, engaged in support services and experienced medication adherence difficulties.Conclusion:Only a small proportion of patients participating in cognitive screening subsequently engaged in diagnostic evaluation, advance planning, or lifestyle changes. However, those with higher risk of cognitive impairment were generally more likely to take some action following cognitive screening. Those at higher risk were also more vulnerable due to greater difficulties with medication adherence.

Importance Subclinical and clinical cardiac diseases have been previously linked to magnetic resonance imaging (MRI) manifestations of cerebrovascular disease, such as lacunes and white matter hyperintensities, as well as dementia. Cortical cerebral microinfarcts (CMIs), a novel MRI marker of cerebral vascular disease, have not been studied, to date, in relation to subclinical and clinical cardiac diseases. Objective To examine the association of blood biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases with CMIs graded on 3-T MRI in a memory clinic population. Design, Setting, and Participants This baseline cross-sectional analysis of a cohort study performed from August 12, 2010, to July 28, 2015, included 464 memory clinic participants. All participants underwent collection of blood samples, neuropsychological assessment, and 3-T MRI. Exposures N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) concentrations were measured by electrochemiluminescence immunoassays. Cardiac disease was defined as a history of atrial fibrillation, ischemic heart diseases, or congestive heart failure. Main Outcomes and Measures The CMIs were graded according to a previously validated protocol. Results Of 464 participants, 124 had insufficient blood plasma samples and 97 had no CMI grading (none, incomplete, or ungradable MRI), leaving a sample size of 243 for final analysis (mean [SD] age, 72.8 [9.1] years; 116 men [42.9%]). Seventy participants (28.8%) had cortical CMIs (median, 1; range, 0-43). Compared with participants with no CMIs, those with CMIs had a significantly higher prevalence of atrial fibrillation (rate ratio [RR], 1.62; 95% CI, 1.20-21.8), ischemic heart disease (RR, 4.31; 95% CI, 3.38-5.49), and congestive heart failure (RR, 2.05; 95% CI, 1.29-3.25). Significantly higher levels of NT-proBNP (RR, 3.16; 95% CI, 2.33-4.27) and hs-cTnT (RR, 2.17; 95% CI, 1.00-4.74) were found in participants with CMIs. In multivariate models adjusted for demographics and vascular risk factors, higher levels of NT-proBNP (RR, 3.19; 95% CI, 2.62-3.90) and hs-cTnT (RR, 4.86; 95% CI, 3.03-7.08) were associated with CMIs. These associations persisted even after excluding patients with clinically manifest cardiac disease. Conclusions and Relevance This study found that biomarkers of subclinical cardiac disease and clinically manifest cardiac diseases were associated with CMIs on 3-T MRI in patients attending a memory clinic, suggesting that cardiac disease may contribute to the development of CMIs. Hence, cardiac dysfunction should be targeted as a potentially modifiable factor to prevent CMI-related brain injury.

Background An AD8 cut-off score of ≥4 has been reported to successfully detect 90% of dementia cases in elderly patients aged 75 years and above. Objective We investigated the benefits of a pilot clinical service conducted in primary care that used the AD8 to identify patients with dementia in an at-risk population. Method Patients ≥75 years of age were recruited from a primary health care center in Singapore. Trained nurses administered the AD8 to informants of eligible patients. Patients screened positive (AD8 score ≥4) were referred to specialist memory clinics by primary health care physicians for further evaluation. Results Of the 551 eligible patients in the primary health care center, 168 (30.5%) consented and the AD8 was administered to their informants. Among the recruited patients, 23 (13.7%) were screened positive and 7 (30.4%) of them accepted referrals to specialist memory clinics. The clinical diagnoses for these patients were as follows: no cognitive impairment (NCI) (n = 1), cognitive impairment no dementia (CIND) (n = 5), and dementia (n = 1). Most of the (98.8%) nurses found AD8 user-friendly and could track functional decline. Eighteen of the 23 (78.3%) primary health care physicians who referred patients to specialist memory clinics considered the AD8 useful for facilitating referrals. The remaining physicians (21.7%) preferred performance-based tests. Conclusion The AD8 is easily administered by nurses and useful to a majority of primary health care physicians to generate referrals. However, physician preference for performance-based tests and a lower prevalence of dementia in the at-risk population may indicate the need to consider a “2-pronged assessment approach” that combines both performance-based and informant-based brief tests to reduce false positive rates and better detect dementia.

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.

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.