Predicting cognitive scores from wearable-based digital physiological features using machine learning: data from a clinical trial in mild cognitive impairment.

BACKGROUND: Continuous assessment and remote monitoring of cognitive function in individuals with mild cognitive impairment (MCI) enables tracking therapeutic effects and modifying treatment to achieve better clinical outcomes. While standardized neuropsychological tests are inconvenient for this purpose, wearable sensor technology collecting physiological and behavioral data looks promising to provide proxy measures of cognitive function. The objective of this study was to evaluate the predictive ability of digital physiological features, based on sensor data from wrist-worn wearables, in determining neuropsychological test scores in individuals with MCI. METHODS: We used the dataset collected from a 10-week single-arm clinical trial in older adults (50-70 years old) diagnosed with amnestic MCI (N = 30) who received a digitally delivered multidomain therapeutic intervention. Cognitive performance was assessed before and after the intervention using the Neuropsychological Test Battery (NTB) from which composite scores were calculated (executive function, processing speed, immediate memory, delayed memory and global cognition). The Empatica E4, a wrist-wearable medical-grade device, was used to collect physiological data including blood volume pulse, electrodermal activity, and skin temperature. We processed sensors' data and extracted a range of physiological features. We used interpolated NTB scores for 10-day intervals to test predictability of scores over short periods and to leverage the maximum of wearable data available. In addition, we used individually centered data which represents deviations from personal baselines. Supervised machine learning was used to train models predicting NTB scores from digital physiological features and demographics. Performance was evaluated using "leave-one-subject-out" and "leave-one-interval-out" cross-validation. RESULTS: The final sample included 96 aggregated data intervals from 17 individuals. In total, 106 digital physiological features were extracted. We found that physiological features, especially measures of heart rate variability, correlated most strongly to the executive function compared to other cognitive composites. The model predicted the actual executive function scores with correlation r = 0.69 and intra-individual changes in executive function scores with r = 0.61. CONCLUSIONS: Our findings demonstrated that wearable-based physiological measures, primarily HRV, have potential to be used for the continuous assessments of cognitive function in individuals with MCI.

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

The splenial angle: a novel radiological index for idiopathic normal pressure hydrocephalus.

OBJECTIVES: To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer's disease (AD), Parkinson's disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans' index and callosal angle. METHODS: Evans' index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed. RESULTS: Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not. CONCLUSIONS: The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention. KEY POINTS: • The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans' index and callosal angle in predicting NPH from healthy, Parkinson's disease, and Alzheimer's disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.

Confluent White Matter in Progression to Alzheimer Dementia.

BACKGROUND: Alongside Alzheimer disease pathology, cerebral small vessel disease (CSVD) contributes to the differential progression rates from mild cognitive impairment (MCI) to dementia. Hence, identification of specific type of CSVD lesions that influence progression is needed. OBJECTIVE: The objective of this study was to evaluate the role of silent CSVD in the progression from MCI to dementia and if confluent white matter hyperintensities (WMHs) pose a higher risk for progression in the clinical setting. METHODS: Patients with MCI with baseline magnetic resonance imaging and longitudinal follow-up were evaluated. WMH were quantified using visual scoring at baseline (all subjects) and at end of study period (subgroup). Influences of baseline total WMH, baseline confluent WMH, and increase of WMH on progression from MCI to dementia were analyzed. RESULTS: A total of 200 patients with a mean age of 67.9 (SD 8.7) years were evaluated. Progression to dementia was significantly higher among patients with MCI with confluent WMH (55.7% vs. 32.3%; P<0.001). The odds ratio of a patient with confluent WMH progressing to dementia was 2.66. The annual decline in Mini Mental State Examination was significantly higher in those with confluent WMH lesions (-1.60 vs. -1.20; P=0.010). In the subgroup with follow-up magnetic resonance imaging (n=70), patients who demonstrated an increase in WMH had greater decline in annual Mini Mental State Examination scores (-1.79 vs. -0.59; P=0.054). CONCLUSION: Confluent WMH lesions in MCI are associated with higher rates of progression to dementia.

Association of Prediabetes and Type 2 Diabetes With Cognitive Function After Stroke: A STROKOG Collaboration Study.

Background and Purpose- Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods- Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1-6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results- Patients with T2D had significantly poorer performance in global cognition (SD, -0.59 [95% CI, -0.82 to -0.36]; P<0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, -0.10 [95% CI, -0.45 to 0.24]; P=0.55) or in any cognitive domain. Conclusions- Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.

Capgras Syndrome in the Young: Schizophrenia or Alzheimer Disease?

This is a case report of an atypical presentation of early onset Alzheimer disease (EOAD) in a young patient with Capgras syndrome and cognitive impairment. The concurrent onset of psychiatric and cognitive symptoms prompted a detailed evaluation for a neurodegenerative disease. A 50-year-old male lawyer presented with low mood, apathy, delusions, and auditory hallucinations over 18 months. He considered his wife as an imposter and would require her text message to confirm her identity. He became more forgetful and had to give up his law practice. His neuropsychological assessment was impaired in all domains. Genetic testing revealed homozygosity for APOEe4 alleles. His magnetic resonance imaging showed predominant parietal and medial temporal atrophy, [18F]Fluorodeoxyglucose positron emission tomography showed frontal, parietal and posterior temporal hypometabolism and [18F]Flutemetamol positron emission tomography was positive for amyloid deposition, leading to the diagnosis of EOAD. This case highlights EOAD as a differential diagnosis in young patients who present with Capgras syndrome.

Interactions Between Acute Infarcts and Cerebrovascular Pathology Predict Poststroke Dementia.

BACKGROUND: Chronic cerebrovascular pathology accelerates the incidence of poststroke dementia (PSD). Whether the risk of PSD varies according to different types of chronic cerebrovascular pathology remains unclear. OBJECTIVES: We investigated whether PSD is associated with a unique pattern of interactions between chronic cerebrovascular pathologies and acute stroke lesions. MATERIALS AND METHOD: In this case-control study of acute mild stroke patients (n=185), cases included patients who developed PSD at a 6-month poststroke follow-up, and controls included patients who remained nondemented at 6 months, matched on prestroke cognitive status. Magnetic resonance imaging was performed at initial stroke presentation; neuropsychological assessments were performed 6 months after the stroke. RESULTS: White matter hyperintensities (WMH), chronic lacunes, microbleeds, and acute infarcts were not associated with PSD after controlling for demographics, cardiovascular risk, and global cortical atrophy. The risk of PSD was largest for patients with acute large subcortical infarcts (>15 mm) and concomitant periventricular WMH compared with patients with large subcortical infarcts and punctate/absent periventricular WMH [odds ratio (OR)=5.85, 95% confidence interval (CI)=1.85-40.04]. A moderate risk of PSD was observed for patients with acute multiple small infarcts (3 to 15 mm) and concomitant lacunes (OR=2.48, 95% CI=0.94-6.51) or concomitant lobar microbleeds (OR=2.20, 95% CI=0.89-5.41), compared with patients with acute multiple small infarcts and absent lacunes or microbleeds. Single small infarcts did not interact with cerebrovascular pathology to affect PSD. CONCLUSIONS: The risk of PSD varies depending on the presence of chronic cerebrovascular pathologies and type of acute infarcts. Clinical implications support a precision medicine approach for stratifying those at highest risk of PSD.

The Longitudinal Impact of Excessive Daytime Somnolence on Motor and Nonmotor Symptoms of Parkinson's Disease in a Southeast Asian Cohort.

OBJECTIVE: Sleep-wake disturbances, such as excessive daytime somnolence (EDS), are nonmotor symptoms of Parkinson's disease (PD) and significantly affect the quality of life. This study aimed to examine the relationship between EDS and motor and nonmotor symptoms of PD. METHODS: Eighty-two patients with idiopathic mild PD were followed up twice a year for 2 years and assessed on sleep, mood, anxiety, cognition, function, and disease severity. Data were analyzed retrospectively, comparing motor and nonmotor outcomes between those with EDS and those without. RESULTS: At baseline, 27.9% had EDS and were similar in demographic and clinical characteristics to those without; 10% had persistent EDS during the first year of follow-up. Excessive daytime somnolence had a significant main effect on mood and anxiety as shown by consistently higher scores on the Geriatric Depression Scale (P = .022) and Hospital Anxiety and Depression Scale-Anxiety subscale scores (P = .011) throughout duration of follow-up. The group with persistent EDS showed greater rate of worsening Frontal Assessment Battery scores by the end of first-year follow-up (P = .025) and greater rate of worsening Apathy Scale scores by the end of 2-year follow-up (P = .002). No significant effects of EDS on motor symptoms and disease severity were found. CONCLUSIONS: In a Southeast Asian cohort of patients with PD, EDS had a negative longitudinal impact on mood, anxiety, apathy, and cognitive function but no impact on motor symptoms and disease severity. Excessive daytime somnolence is thus a potential therapeutic target to improve nonmotor outcomes.

Suicidal ideation is common in autosomal dominant Alzheimer's disease at-risk persons.

OBJECTIVES: To study the frequency of suicidal ideation and its association with clinical and neurobiological correlates among cognitively intact autosomal dominant Alzheimer's disease (ADAD) at-risk individuals. METHODS/DESIGN: In a cross-sectional study of 183 ADAD at-risk individuals (91 mutation carriers and 92 noncarriers), we compared the frequency of suicidal ideation among carriers and noncarriers. Linear mixed-effects models with family-level random effects evaluated the relationships between geriatric depression scale (GDS), neuropsychiatric inventory-questionnaire (NPI-Q), and suicidal ideation scores among all ADAD at-risk individuals. An interaction term was added to the regression models to evaluate the interactions of suicidal ideation and mutation status on neuropsychiatric symptoms. RESULTS: Twenty-six (14.20%) ADAD at-risk individuals (13 [14.28%] carriers and 13 [14.13%] noncarriers) had suicidal ideation. The frequency of suicidal ideation did not differ between carriers and noncarriers. Suicidal ideation was associated with higher GDS among all ADAD at-risk individuals. When stratified into mutation carrier status, noncarriers with suicidal ideation had higher GDS than carriers. There was no statistically significant association between suicidal ideation and NPI-Q among ADAD at-risk individuals. Awareness of mutation status, neuropsychological performances, and cerebrospinal fluid AD biomarkers were not associated with suicidal ideation among carriers and noncarriers. CONCLUSIONS: Suicidal ideation is common among cognitively intact ADAD at-risk individuals. While ADAD at-risk individuals with suicidal ideation have greater depressive symptoms, noncarriers with suicidal ideation have higher GDS scores than carriers. Interestingly, awareness of the mutation status was not associated with suicidal ideation in our study. Early identification of suicidal thoughts can facilitate timely interventions to prevent suicidal behaviours. Keywords autosomal dominant Alzheimer's diseasedominantly inherited Alzheimer's networkneuropsychiatric symptomssuicidal ideation.

Construct validity of the Visual Cognitive Assessment Test (VCAT)-a cross-cultural language-neutral cognitive screening tool.

BACKGROUND: The Visual Cognitive Assessment Test (VCAT) is a language-neutral cognitive screening tool designed for use in culturally diverse populations without the need for translations or adaptations. While it has been established to be language-neutral, the VCAT's construct validity has not been investigated. METHODS: 471 participants were recruited, comprising 233 healthy comparisons, 117 mild cognitive impairment (MCI), and 121 mild Alzheimer's disease (AD) patients. VCAT and domain-specific neuropsychological tests were administered in the same sitting. Construct validity was assessed by analyzing domain-specific associations between the VCAT and well-established cognitive assessments. Reliability (internal consistency) was measured by Cronbach's alpha. Diagnostic ability (area under the curve) and recommended cutoffs were determined by receiver operating characteristic (ROC) analysis. RESULTS: The VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α = .74). ROC analysis found that the VCAT was on par with the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at distinguishing between healthy comparisons, MCI, and mild AD. Consistent with previous studies, VCAT scores were not affected by language of administration or ethnicity in our cohort. Findings suggest the following cutoffs: Dementia 0-19, MCI 20-24, Normal 25-30. CONCLUSION: This study established the construct validity of the VCAT, which is vital to ensure its subdomains effectively measure the cognitive processes they were designed to. The VCAT is capable of detecting early cognitive impairments and allows for meaningful cross-cultural comparisons, especially useful for international collaborations and clinical trials, and for clinical use in diverse multiethnic populations.

Does health-related quality of life in Asian informal caregivers differ between early-onset dementia and late-onset dementia?

AIM: Early-onset dementia (EOD) (defined as dementia onset before age 65) presents specific challenges and issues, adding to the negative impact of dementia on the health-related quality of life (HRQOL) of both patients and their caregivers. However, very few published studies have specifically compared the HRQOL of caregivers of people with EOD and late-onset dementia (LOD). This information is critical in allocating and prioritizing scarce health-care resources. We aimed to assess the HRQOL of primary informal caregivers of community-dwelling individuals with EOD in Singapore and compare it with that of caregivers of individuals with LOD. METHODS: This was a cross-sectional study of consecutive patient-caregiver dyads from a tertiary dementia clinic. RESULTS: No significant differences in disease severity were found between the 111 EOD and 235 LOD patient-caregiver dyads. The mean Mental Component Summary score of the 36-item Short-Form Health Survey version 2 was significantly worse in caregivers of EOD patients than in LOD caregivers (mean: 41.42 vs 45.12, P = 0.001), although the mean Physical Component Summary scores were comparable (49.71 vs 49.53, P = 0.934). However, the impact of dementia early onset on caregivers' mental health diminished immediately after adjustment for the disease severity indicators, of which the Neuropsychiatric Inventory Questionnaire distress score was the only significant clinical factor (regression coefficient ß = -0.29, P < 0.001). The amount of variability in the HRQOL of the caregivers explained by patient and caregiver factors across all the models was rather small (adjusted R2 = 19.3% for the Mental Composite Score, 5.2% for Physical Composite Score). CONCLUSION: Caregivers of EOD patients had worse mental health than LOD caregivers probably because individual with EOD have more behavioural disturbances. This reinforces the indispensable role of managing behavioural problems when caring for a family member with dementia, especially for EOD. HRQOL ideally needs to be assessed based on self-report rather than inferences from indirect data such as the subjective caregiver burden.

Hippocampal subfield atrophy of CA1 and subicular structures predict progression to dementia in idiopathic Parkinson's disease.

BACKGROUND: Global hippocampal atrophy is a hallmark of Alzheimer's dementia and has been similarly reported in Parkinson's disease dementia (PDD). However, there is limited literature on the differential involvement of hippocampal subfields in predicting conversion to PDD. This study is an extension of previous findings on progression to mild cognitive impairment in Parkinson's disease (PD). METHODS: This cohort study recruited 73 non-demented participants with idiopathic PD (age 65.80±8.17, 75.3% male) from an outpatient neurology clinic. All participants underwent clinical assessment, neuropsychological testing and 3T MRI scans at baseline and 18 months while on prescribed dopaminergic medication. Hippocampal subfield volumes were obtained using automatic segmentation in FreeSurfer V.6.0. Participants who progressed to PDD and those who did not were compared on hippocampal subfield atrophy and cognitive change (episodic memory, attention, executive functions, language, visuospatial abilities). Subfields were further examined for their abilities to predict PDD conversion and distinguish PDD from non-demented PD using receiver operating characteristic analysis. RESULTS: Smaller baseline global hippocampal volume, cornu ammonis (CA) subfield CA1, subiculum and presubiculum volumes were observed in participants who went on to develop dementia, and predicted PDD conversion. Those who progressed to PDD saw greater decline in global hippocampal volume, granule cell layer of the dentate gyrus, presubiculum, parasubiculum and fimbria. Decline in subiculum and fimbria volume corresponded to cognitive decline in attention and executive functions, respectively. CONCLUSIONS: Early atrophy of CA1, subiculum and presubiculum preceded, and predicted, PDD conversion. Differential patterns of subfield atrophy were also observed among those who progressed to PDD and were associated with impaired executive functions.

Mechanisms Linking White Matter Lesions, Tract Integrity, and Depression in Alzheimer Disease.

OBJECTIVE: Late-life depression involves the disconnection of white matter tracts that regulate mood. A pathogenic link between poor tract integrity and depressive symptoms is believed to be white matter lesions (WML), however the mechanisms linking tract integrity, WML, and depression remains unexplored. The authors sought to identify whether the association between reduced tract integrity and depressive symptoms is mediated by WML in patients with Alzheimer disease (AD), and whether individual characteristics moderate this effect. METHODS: This was a cross-sectional study in a tertiary memory clinic. A total of 91 patients with mild AD and 79 healthy elderly, comparable in depressive symptoms, white matter hyperintensities (WMH) volume, cardiovascular risk, age, and sex were chosen. Tract integrity was assessed using diffusion tensor imaging, WML were indexed as WMH, measured using fluid-attenuation inversion recovery imaging, and depressive symptoms were measured with the informant-based Geriatric Depression Scale. RESULTS: In patients with mild AD, reduced tract integrity in right hemispheric cortical-subcortical tracts and the genu of the corpus callosum was moderately associated with depressive symptoms. This association was fully mediated by WML. Moderation analysis indicated that old age strengthened the association between all tracts and depressive symptoms, as mediated by WML. In cognitively healthy elderly, neither tracts nor WML were related to depressive symptoms. CONCLUSION: Reduced tract integrity may be important but not sufficient for the manifestation of depressive symptoms in mild AD. Instead, WML may drive the pathogenic link between reduced tract integrity and depressive symptoms.

Mapping the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory to the Health Utility Index Mark III.

PURPOSE: To map the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) to the Health Utility Index Mark III (HUI3) in people living with dementia (PWD) and to compare the performance of five methods for mapping. METHODS: A cross-sectional study of 346 dyads of community-dwelling PWD and family caregiver was carried out in Singapore. ADCS-ADL and HUI3 were rated by the family caregivers. Disease severity ratings and Mini Mental State Examination (MMSE) results were retrieved from medical records. A recently proposed mapping method called the Mean Rank Method (MRM) was described and applied, and the results were compared with regression-based mapping, including ordinary least squares, censored least absolute deviation (CLAD), Tobit and response mapping. RESULTS: The MRM produced a mapped utility distribution that closely resembled the observed utility distribution. The standard deviations (SDs) of the observed and MRM-mapped utility were both 0.340, whereas the SDs of the other mapped utilities ranged from 0.243 (response mapping) to 0.283 (CLAD). Regressing the MRM- and CLAD-mapped and observed utility values upon disease severity and MMSE gave similar regression lines (each P > 0.05). Regressing the other mapped utility values upon the covariates under- (over-) estimated the utility of good (poor) clinical states. However, regression-based mapping methods gave a better fit at the individual level, as measured by root mean square error, mean absolute error and R2. K fold cross-validation gave similar results. CONCLUSIONS: The MRM is accurate at the group level. The regression-based mapping methods are more accurate for making individual-level prediction. In addition, CLAD also performed reasonably well at the group level.

Dyslexic Characteristics of Chinese-Speaking Semantic Variant of Primary Progressive Aphasia.

Reading disorder is a recognized feature in primary progressive aphasia (PPA). Surface dyslexia, characterized by regularization errors, is typically seen in the English-speaking semantic variant of PPA (svPPA). However, dyslexic characteristics of other languages, particularly logographical languages such as Chinese, remain sparse in the literature. This study aims to characterize and describe the dyslexic pattern in this group of patients by comparing an English-speaking svPPA group with a Chinese-speaking svPPA group. The authors hypothesized that Chinese-speaking individuals with svPPA would likely commit fewer surface dyslexic errors. By accessing the database of Singapore's National Neuroscience Institute and the National Alzheimer's Coordinating Center of the United States, the authors identified three Chinese-speaking and 18 English-speaking patients with svPPA, respectively, for comparison. The results suggest that, instead of surface dyslexia, svPPA in Chinese-speaking individuals is characterized by a profound deep dyslexic error. Based on current evidence suggesting the role of the temporal pole as a semantic convergence center, the authors conclude that this region also mediates and converges lexical-semantic significance in logographical languages.

Neuropsychiatric symptoms in South-East Asian patients with mild cognitive impairment and dementia: prevalence, subtypes, and risk factors.

BACKGROUND: The subtypes and risk factors of neuropsychiatric symptoms remain largely unexplored in South-East Asian populations. OBJECTIVE: We investigated the prevalence, subtypes, and risk factors, namely, demographic, medical morbidity, and cognitive impairment associated with neuropsychiatric symptoms in a South-East Asian cohort of patients with mild cognitive impairment (MCI) and dementia. METHODS: A clinical cohort of 38 MCI and 198 mild-moderate dementia patients were assessed using the Neuropsychiatric Inventory-Questionnaire. RESULTS: Neuropsychiatric symptoms were equally prevalent among patients with MCI (74%) and mild-moderate dementia (85%). Three subtypes of symptoms were identified for each diagnostic group; for MCI, they included mood disturbances, anxiety/sleep problems, and psychosis, while for dementia, the subtypes included behavioral disturbances, psychosis/mood, and hyperactive behaviors. The largest risk for neuropsychiatric symptoms for both MCI and dementia patients was male gender. Among patients with MCI, burden of cerebrovascular disease and global cognitive impairment were small risks for neuropsychiatric symptoms, while for patients with dementia, an older age (>65 years) was a small risk and lower educational attainment was a moderate risk. DISCUSSION: These findings contribute to the worldwide epidemiology of neuropsychiatric symptoms in MCI and dementia and highlight that the profile of symptoms, subtypes, and risks is fairly homogenous across Western and Asian cultures. Copyright © 2017 John Wiley & Sons, Ltd.

Depressive symptoms influence global cognitive impairment indirectly by reducing memory and executive function in patients with mild cognitive impairment.

BACKGROUND: Depressive symptoms negatively influence global cognition in the elderly; however, the mechanism of this effect remains unclear. OBJECTIVE: To investigate whether depressive symptoms influence global cognitive function in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) by impeding specific neuropsychological abilities and under what conditions this effect might occur. METHOD: A sample of 259 participants (104 cognitively normal elderly controls, 66 patients with MCI and 89 patients with mild AD) underwent a comprehensive neuropsychological assessment. Global cognitive impairment was indexed by the composite of Mini-Mental State Examination and Montreal Cognitive Assessment scores and severity of depressive symptoms was measured with the Geriatric Depression Scale (GDS). RESULTS: Among patients with MCI, greater severity of depressive symptoms was associated with greater global cognitive impairment, with a moderate effect size. A mediation analysis revealed that patients with MCI experiencing depressive symptoms may exhibit global cognitive impairment because their depressive symptoms were reducing their capacity for working memory, episodic memory and non-speed-based executive functions. A moderation analysis indicated that this effect was consistent across age, gender, years of education and APOE-e4 status for working memory and episodic memory, and was observed in patients with MCI older than 65 years for executive functions. In cognitively normal elderly adults and patients with AD, depressive symptoms were not associated with global cognitive impairment. CONCLUSIONS: Depressive symptoms influence global cognitive function in patients with MCI indirectly by reducing mental space, mental flexibility and their capacity for consolidating and retrieving memories. These findings may guide clinicians to better diagnose and manage cognitive impairment in the context of concomitant depressive symptoms.

Early detection of dementia in multilingual populations: Visual Cognitive Assessment Test (VCAT).

BACKGROUND: Early diagnosis of cognitive impairment allows timely intervention with pharmacological and non-pharmacological measures. However, current cognitive evaluation tools do not cater for multilingual populations. OBJECTIVE: To develop and validate a visual-based cognitive evaluation tool, the Visual Cognitive Assessment Test (VCAT), which can be administered to multilingual populations without the need for translation or adaptation. METHOD: We designed a battery of tests to evaluate the domains of memory, executive function, visuospatial function, language and attention. Pilot testing of individual test items, followed by test refinement and development of a field version was performed. We subsequently validated VCAT for the diagnosis of mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Diagnostic performance was assessed by the area under the curve (AUC), sensitivity (Se) and specificity (Sp). RESULTS: VCAT was validated in a sample of 206 participants. The sample comprised 53.9% males; mean age (SD) was 67.8 (8.86) years; mean years of education was 10.5(6.0). AUC of VCAT for detection of cognitive impairment was found to be 93.3 (95% CI 90.1 to 96.4). Also, the Se and Sp of VCAT for the diagnosis of cognitive impairment (MCI and mild AD) were 85.6% and 81.1%, respectively. VCAT's diagnostic Se and Sp comparable to those of the Montreal Cognitive Assessment in the same cohort. Mean time-to-complete VCAT was 15.7 ± 7.3 min. CONCLUSIONS: The VCAT has good Se and Sp for the diagnosis of MCI and mild AD. The visual-based test paradigm allows easy application to multilingual populations without the need for translation or adaptation.

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 MoCA's 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 MoCA's 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 MoCA's 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 (η(2) = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η(2) = 0.115 and η(2) = 0.162, respectively). CONCLUSION: The MoCA's 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.