MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET (11C-PIB, 18F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.

Correction: Electronic Cognitive Screen Technology for Screening Older Adults With Dementia and Mild Cognitive Impairment in a Community Setting: Development and Validation Study.

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Electronic Cognitive Screen Technology for Screening Older Adults With Dementia and Mild Cognitive Impairment in a Community Setting: Development and Validation Study.

BACKGROUND: A digital cognitive test can be a useful and quick tool for the screening of cognitive impairment. Previous studies have shown that the diagnostic performance of digital cognitive tests is comparable with that of conventional paper-and-pencil tests. However, the use of commercially available digital cognitive tests is not common in Hong Kong, which may be due to the high cost of the tests and the language barrier. Thus, we developed a brief and user-friendly digital cognitive test called the Electronic Cognitive Screen (EC-Screen) for the detection of mild cognitive impairment (MCI) and dementia of older adults. OBJECTIVE: The aim of this study was to evaluate the performance of the EC-Screen for the detection of MCI and dementia in older adults. METHODS: The EC-Screen is a brief digital cognitive test that has been adapted from the Rapid Cognitive Screen test. The EC-Screen uses a cloud-based platform and runs on a tablet. Participants with MCI, dementia, and cognitively healthy controls were recruited from research clinics and the community. The outcomes were the performance of the EC-Screen in distinguishing participants with MCI and dementia from controls, and in distinguishing participants with dementia from those with MCI and controls. The cohort was randomly split into derivation and validation cohorts based on the participants' disease group. In the derivation cohort, the regression-derived score of the EC-Screen was calculated using binomial logistic regression. Two predictive models were produced. The first model was used to distinguish participants with MCI and dementia from controls, and the second model was used to distinguish participants with dementia from those with MCI and controls. Receiver operating characteristic curves were constructed and the areas under the curves (AUCs) were calculated. The performances of the two predictive models were tested using the validation cohorts. The relationship between the EC-Screen and paper-and-pencil Montreal Cognitive Assessment-Hong Kong version (HK-MoCA) was evaluated by the Pearson correlation coefficient. RESULTS: A total of 126 controls, 54 participants with MCI, and 63 participants with dementia were included in the study. In differentiating participants with MCI and dementia from controls, the AUC of the EC-Screen in the derivation and validation cohorts was 0.87 and 0.84, respectively. The optimal sensitivity and specificity in the derivation cohorts were 0.81 and 0.80, respectively. In differentiating participants with dementia from those with MCI and controls, the AUC of the derivation and validation cohorts was 0.90 and 0.88, respectively. The optimal sensitivity and specificity in the derivation cohort were 0.83 and 0.83, respectively. There was a significant correlation between the EC-Screen and HK-MoCA (r=-0.67, P<.001). CONCLUSIONS: The EC-Screen is suggested to be a promising tool for the detection of MCI and dementia. This test can be self-administered or assisted by a nonprofessional staff or family member. Therefore, the EC-Screen can be a useful tool for case finding in primary health care and community settings.

Can transcranial Doppler ultrasound be used for screening cerebral small vessel diseases in the community?

OBJECTIVES: Elderly persons harbouring severe white matter hyperintensity (WMH), a radiological manifestation of cerebral small vessel disease (SVD), have an increased risk of dementia, stroke and poor functional outcomes. A simple screening tool will enhance their recruitment into preventive trials for SVD. We explored the clinical utility of the pulsatility index (PI) of the middle cerebral artery (MCA), obtained from transcranial Doppler ultrasound (TCD), in identifying severe WMH among community elderly persons with vascular risk factors. METHODS: Three hundred and thirty-one dementia- and stroke-free community elderly subjects with hypertension and/or diabetes mellitus underwent TCD to obtain the MCA PI. The WMH volume on 3.0 Tesla MRI was quantified and normalized to each subject's brain volume. The normalized WMH volumes were classified as low (<14.5 ml, 1 standard deviation [SD] above the mean, 84th percentile) or high (≥14.5 ml). The severity of WMH was also rated visually with the Fazekas score. Logistic regression and receiver-operator characteristics (ROC) analysis were performed to evaluate the association between the MCA PI and the severity of WMH. RESULTS: The MCA PI was not an independent predictor of severe WMH. An MCA PI ≥1.095 detected high normalized WMH volumes with an area under the curve (AUC) of 0.553 (95% CI 0.473-0.633), sensitivity of 0.556, and specificity of 0.523. ROC analysis of the MCA PI in predicting high Fazekas scores yielded similar findings. CONCLUSION: In stroke- and dementia-free elderly persons with vascular risk factors, the MCA PI was unable to identify severe WMH. (Word count: 260).

Lower Urinary Tract Symptoms in Subjects with Subclinical Cerebral White Matter Lesions.

AIM: We assessed the impact of cerebral white matter lesions (WMLs) on lower urinary tract symptoms in subjects with normal neurological and cognitive function. METHODS: A cohort of community-dwelling subjects aged ≥65 years were recruited to undergo MRI brain assessment. WMLs were graded using the Fazekas scale from 0 to 3. A separate telephone interview was carried out to assess the urinary symptoms in these subjects using the questionnaire Overactive Bladder-Validated 8-Question Awareness Tool (OAB-V8). RESULTS: 800 community-dwelling elderly subjects were recruited to undergo MRI brain. In this cohort, 431 subjects responded to the telephone interview concerning their urinary symptoms. Among the respondents, 21.1% did not exhibit any WML on their MRI brain. Most of the subjects (52.6%) exhibited grade 1 WML. On logistic regression, age was found to be positively correlated with the Fazekas score (correlation coefficient 0.203, p ≤ 0.01). Using a cutoff of 8 on OAB-V8, 22% of the respondents experienced OAB. Presence of WML, hypertension, or diabetes mellitus was not found to be correlated with storage urinary symptoms or OAB-V8 total score. Multiple logistic regression analysis did not show the presence of WML to be associated with the diagnosis of OAB (adjusted OR 1.13, 95% CI 0.65-1.96, p=0.659). CONCLUSIONS: WML is associated with age and is common in the elderly population. Mild WML is subclinical, with no obvious neurological and urinary symptoms. Our cohort did not demonstrate a relationship between WML and lower urinary tract symptoms.

The efficacy and safety of the Chinese herbal medicine Di-Tan decoction for treating Alzheimer's disease: protocol for a randomized controlled trial.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia in the elderly. It is estimated that the global prevalence of dementia will rise from 24.3 million in 2005 to 81.1 million in 2040. AD has a devastating impact on sufferers, caregivers, their communities and the healthcare system in general. "Di-tan decoction" (DTD) is a traditional Chinese medicine (TCM) formula frequently used to treat symptoms that are now defined as AD in clinical treatment. However, the existing evidence for recommending DTD in clinical practice derives from studies that were methodologically flawed. In this study, we aim to determine the efficacy and safety of DTD in AD patients based on a rigidly randomized controlled trial. It will provide critical information on sample size and treatment regimen for conducting a full-scale clinical trial of DTD later. METHODS/DESIGN: This study will be a double-blind, randomized, placebo-controlled, add-on trial. After a 2-week run-in period, eligible patients with mild to moderate AD will be recruited and given either DTD or placebo twice daily for 24 weeks with follow-up 6 weeks after the last treatment. An increase of four points or greater on the scores of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAD-cog) will be considered as a positive primary outcome. Total scores of the ADAD-cog, the Chinese version of Mini-Mental State Examination (C-MMSE), and the Chinese version of the Disability Assessment for Dementia (C-DAD) score will be used as secondary outcomes. Adverse events will also be reported. DISCUSSION: This randomized trial will be the first rigorous empirical study on the efficacy of DTD for treating cognitive symptoms in AD patients. Its success will justify and warrant a large-scale clinical trial to further consolidate the evidence for DTD's efficacy in treating AD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( ChiCTR-TRC-12004548 , Date of registration: 22 November 2012).

Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization working group proposed a brief cognitive protocol for screening of vascular cognitive impairment. We investigated the validity, reliability, and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-minute protocol) administered over the telephone. METHODS: Four items examining attention, verbal learning and memory, executive functions/language, and orientation were extracted from the MoCA to form the MoCA 5-minute protocol. One hundred four patients with stroke or transient ischemic attack, including 53 with normal cognition (Clinical Dementia Rating, 0) and 51 with cognitive impairment (Clinical Dementia Rating, 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-minute protocol over the telephone. RESULTS: Administration of the MoCA 5-minute protocol took 5 minutes over the telephone. Total score of the MoCA 5-minute protocol correlated negatively with age (r=-0.36; P<0.001) and positively with years of education (r=0.41; P<0.001) but not with sex (ρ=0.03; P=0.773). Total scores of the MoCA and MoCA 5-minute protocol were highly correlated (r=0.87; P<0.001). The MoCA 5-minute protocol performed equally well as the MoCA in differentiating patients with cognitive impairment from those without (areas under receiver operating characteristics curve for MoCA 5-minute protocol, 0.78; MoCA=0.74; P>0.05 for difference; Cohen d for group difference, 0.80-1.13). It differentiated cognitively impaired patients with executive domain impairment from those without (areas under receiver operating characteristics curve, 0.89; P<0.001; Cohen d=1.7 for group difference). Thirty-day test-retest reliability was excellent (intraclass correlation coefficient, 0.89). CONCLUSIONS: The MoCA 5-minute protocol is a free, valid, and reliable cognitive screen for stroke and transient ischemic attack. It is brief and highly feasible for telephone administration.

Validity and reliability of the neuropsychiatric inventory questionnaire version in patients with stroke or transient ischemic attack having cognitive impairment.

This study examined the validity and reliability of the Neuropsychiatric Inventory Questionnaire version (NPI-Q), a proxy-reported format of the interview-based NPI, in assessing neuropsychiatric symptoms in 173 patients with stroke or transient ischemic attack (TIA) having cognitive impairment. The NPI-Q was validated against the NPI as a gold standard. Informants took approximately 7 minutes to complete the NPI-Q. Bland-Altman analysis revealed a bias of 0.7 points, with 95% limits of agreement between -8.6 and 10.0 between the total symptom scores of the NPI and NPI-Q. The NPI-Q correlated significantly with the NPI in individual and total symptom scores and caregiver distress scores. In predicting presence of symptoms on the NPI, the NPI-Q yielded, on average, sensitivity of 74.1% and specificity of 79.5%. On the NPI-Q, informants tended to overreport symptoms in patients with less severe symptoms but underreport with increasing symptom severity. Internal consistency of the NPI-Q was acceptable (Cronbach's α = 0.756). One-week test-retest reliability of the NPI-Q was excellent (intraclass correlation coefficient = .990). The NPI-Q is a valid and reliable instrument for screening neuropsychiatric symptoms in patients with stroke and TIA.

The NINDS-Canadian stroke network vascular cognitive impairment neuropsychology protocols in Chinese.

BACKGROUND AND PURPOSE: Vascular cognitive impairment (VCI) affects up to half of stroke survivors and predicts poor outcomes. Valid and reliable assessement for VCI is lacking, especially for the Chinese population. In 2005, the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) Harmonisation workshop proposed a set of three neuropsychology protocols for VCI evaluation. This paper is to introduce the protocol design and to report the psychometric properties of the Chinese NINDS-CSN VCI protocols. METHODS: Fifty patients with mild stroke (mean National Institute of Health Stroke Scale 2.2 (SD=3.2)) and 50 controls were recruited. The NINDS-CSN VCI protocols were adapted into Chinese. We assessed protocols' (1) external validity, defined by how well the protocol summary scores differentiated patients from controls using receiver operating characteristics (ROC) curve analysis; (2) concurrent validity, by correlations with functional measures including Stroke Impact Scale memory score and Chinese Disability Assessment for Dementia; (3) internal consistency; and (4) ease of administration. RESULTS: All three protocols differentiated patients from controls (area under ROC for the three protocols between 0.77 to 0.79, p<0.001), and significantly correlated with the functional measures (Pearson r ranged from 0.37 to 0.51). A cut-off of 19/20 on MMSE identified only one-tenth of patients classified as impaired on the 5-min protocol. Cronbach's α across the four cognitive domains of the 60-min protocol was 0.78 for all subjects and 0.76 for stroke patients. CONCLUSIONS: The Chinese NINDS-CSN VCI protocols are valid and reliable for cognitive assessment in Chinese patients with mild stroke.

The validity, reliability and clinical utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease.

BACKGROUND/AIMS: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). METHODS: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. RESULTS: Performance on the HK-MoCA was significantly predicted by both executive (beta = 0.23, p = 0.013) and non-executive (beta = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. CONCLUSION: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.