Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region.

BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia. METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available. RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.

A randomized controlled trial of self-regulated modified constraint-induced movement therapy in sub-acute stroke patients.

BACKGROUND AND PURPOSE: Emerging research suggests the use of self-regulation (SR) for improving functional regain in patients post stroke. SR is proposed to produce an added effect to effective modified constraint-induced movement therapy (mCIMT). This study aimed to examine the effect of a self-regulated mCIMT programme (SR-mCIMT) for functional regain in patients with sub-acute stroke. METHODS: Eighty-six patients completed the trial: SR-mCIMT, n = 29; mCIMT, n = 31; or conventional functional rehabilitation, n = 26. All interventions were 2-week therapist-guided training. Outcome measurements, taken by a blinded assessor, examined arm function [Action Research Arm Test (ARAT), Fugl-Meyer Assessment (FMA)], daily task performance [Lawton Instrumental Activities of Daily Living Scale (Lawton IADL)] and self-perceived arm use in functional tasks [Motor Activity Log (MAL)]. RESULTS: Significant differences were found with the SR-mCIMT outperforming the other groups after the intervention (ARAT, P = 0.006; FMA, Lawton IADL and MAL, all Ps < 0.001). In terms of the carry-over effect, the SR-mCIMT group outperformed in the hand and coordination subscales of ARAT and FMA (P = 0.012-0.013) and the self-perceived quality of arm use (P = 0.002). CONCLUSION: A combination of SR and mCIMT could produce an added effect in functional regain in patients post stroke.

Hong Kong College of Physicians Position Statement and Recommendations on the 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the Management of Arterial Hypertension.

The American College of Cardiology/American Heart Association released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults in 2017. In 2018, the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) published new guidelines for the management of arterial hypertension. Despite the many similarities between these two guidelines, there are also major differences in the guidelines in terms of diagnosis and treatment of hypertension. A working group of the Hong Kong College of Physicians (HKCP) convened and conducted a focused discussion on important issues of public interest, including classification of BP, BP measurement, thresholds for initiation of antihypertensive medications, BP treatment targets, and treatment strategies. The HKCP concurs with the 2018 ESC/ESH guideline on BP classification, which defines hypertension as office systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. The HKCP also acknowledges the growing evidence of home BP monitoring and ambulatory BP monitoring in the diagnosis and monitoring of hypertension and endorses the wider use of both methods. The HKCP also supports the direction of a risk-based approach for initiation of antihypertensive medications and the specification of a treatment target range for both systolic and diastolic BP with consideration of different age-groups and specific disease subgroups. Non-pharmacological interventions are crucial, both at the societal and individual patient levels. The recent guideline publications provide good opportunities to increase public awareness of hypertension and encourage lifestyle modifications among the local population.

Pontine microbleeds and depression in stroke.

OBJECTIVES: Depression is the most common affective disorder following stroke yet the neuroanatomical model of poststroke depression (PSD) remains unclear. This study examined the association between PSD and cerebral microbleeds (CMBs) and hypothesized that CMBs in specific regions would be associated with PSD. METHODS: Of the 4766 patients with first ever or recurrent acute ischemic stroke admitted to the Acute Stroke Unit of the Prince of Wales Hospital between June 2004 and October 2010, 229 met the entry criteria and formed the study sample. Patients with a Geriatric Depression Scale score of 7 or above were classified as having PSD. The presence and location of CMBs were evaluated with magnetic resonance imaging. RESULTS: Compared to the non-PSD group, patients with PSD were more likely to have pontine CMBs (32.0% vs 18.2%; P = .019). The presence of pontine CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 2.2 (P = .016). CONCLUSION: The results suggest that pontine CMBs are associated with a higher risk of developing PSD.

Location of infarcts and apathy in ischemic stroke.

BACKGROUND: Apathy is common in stroke survivors. Unlike poststroke depression, apathy after stroke has not been extensively investigated and the significance of the location of infarcts in the development of apathy following a stroke is unknown. This study examined the association between poststroke apathy (PSA) and the location of infarcts. METHODS: A cohort of 185 patients with acute ischemic stroke admitted to the Stroke Unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a psychiatrist administered the Apathy Evaluation Scale (AES). PSA was defined as an AES score of 37 or above. The presence and location of infarcts were evaluated with magnetic resonance imaging. RESULTS: Altogether 185 patients met the entry criteria and formed the study sample; 20 (10.8%) had PSA. PSA patients were older and had higher stroke severity and more depressive symptoms. The PSA group also had lower levels of physical and cognitive functioning. Compared with the non-PSA group, PSA patients were more likely to have acute pontine infarcts (35.0% vs. 11.5%; p = 0.011). They had a higher mean number (0.5 ± 0.7 vs. 0.1 ± 0.3; p = 0.003) and larger volume (0.6 ± 1.4 vs. 0.1 ± 0.3 ml; p = 0.002) of acute pontine infarcts. Six variables were entered into the predictive regression model: age, the presence, number and volume of acute pontine infarcts, the number of old infarcts and periventricular white matter hyperintensities scores. The volume of infarcts remained an independent predictor of PSA in the multivariate analysis, with an odds ratio of 3.9 (p = 0.007). The Geriatric Depression Scale, National Institutes of Health Stroke Scale, Barthel Index and Mini-Mental State Examination scores were also entered into the subsequent associative regression model; the volume of acute pontine infarcts remained a significant predictor (odds ratio = 3.8). CONCLUSIONS: This is the first report of an association between pontine infarcts and the risk of PSA. The results suggest that pontine infarcts may play a role in the development of PSA. The importance of acute pontine infarcts in the pathogenesis of PSA warrants further investigation.

White matter hyperintensities and quality of life in acute lacunar stroke.

White matter hyperintensities (WMH) are common in stroke. The influence of WMH on health-related quality of life (HRQoL) following a lacunar stroke is unknown. This study evaluated the impact of WMH on HRQoL in acute lacunar stroke. A cohort of 160 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a research assistant administered the Short Form-36 (SF-36) to assess HRQoL. The severity of WMH was evaluated with magnetic resonance imaging (MRI). In univariate analysis, the severity of deep WMH (DWMH) negatively correlated with patients' vitality (VT; p < 0.05), social function (SF; p < 0.001), role-emotional (RE; p < 0.01), mental health (MH; p < 0.01), and mental component summary (MCS; p < 0.001) scores of HRQoL. DWMH was independently associated with all of the above five SF-36 scores (p < 0.05) in linear regression analysis. These findings suggest that DWMH has a significant impact on the HRQoL of stroke survivors. The importance of DWMH in the long-term HRQoL in lacunar stroke warrants further investigation.

Serotonin receptor 2C gene polymorphism associated with post-stroke depression in Chinese patients.

The serotonin receptor 2C (HTR2C) gene has been shown to play a pivotal role in major depression. We examined the association between post-stroke depression (PSD) and polymorphism in HTR2C. A cohort of 223 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a geriatric depression scale score of 7 or above. Possible confounding factors, including previous history of stroke, severity of stroke, level of social support, and recent life events, were investigated. All patients were genotyped for polymorphisms of HTR2C. Separate analyses were performed for males and females. Sixty-one patients were found to have PSD. There were significant associations between the HTR2C gene and PSD status in the male patients, but not in the female ones. After adjusting for possible confounders, the rs12837651 T allele (odds ratio = 4.020) and the rs2192371 G allele (odds ratio = 2.866) were found to be significantly associated with PSD in males. Genetic variation in HTR2C receptors appears to be involved in the pathogenesis of PSD in Chinese males.

Cerebral microbleeds and depression in lacunar stroke.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) are common in stroke survivors and the community-dwelling elderly. The clinical significance of CMB in the development of depression after a stroke is unknown. This study examined the association between poststroke depression (PSD) and CMB. METHODS: A cohort of 235 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the onset of the index stroke, a research assistant administered the locally validated 15-item Geriatric Depression Scale. PSD was defined as a Genetic Depression Scale score of ≥7. The presence and location of CMB were evaluated with MRI. RESULTS: In comparison with the non-PSD group, PSD patients were more likely to have lobar CMB (33.3% versus 19.9%; P=0.022). Lobar CMB remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 2.08 (P=0.032). CONCLUSIONS: The results suggest that lobar CMB may play a role in the development of PSD. The importance of CMB in the pathogenesis of depression in stroke survivors and the general elderly population warrants further investigation.

Operational definitions improve reliability of the age-related white matter changes scale.

BACKGROUND AND PURPOSE: Although the age-related white matter changes (ARWMC) scale has been advocated to be applicable to both MRI and CT for assessing the severity of WMC, its inter-rater reliability on CT is only fair. We aimed to operationalize the ARWMC scale and investigate the effect of this operationalization on the reliability and validity on MRI and CT. METHODS: Operational definitions of the ARWMC scale were derived from Erkinjuntti research criteria for subcortical vascular dementia and Scheltens scale. Using original and operationalized ARWMC scale, eight observers recorded the time for rating per MRI and per CT. We investigated the inter-rater and intrarater reliability as well as validity against volume using data from 97 stroke patients. RESULTS: Inter-rater reliability of the operationalized scale on CT (0.874, 95% confidence interval [0.780-0.934]) was better than the original scale (0.569, 95% confidence interval [0.247-0.775]). Its intrarater reliability on CT (0.869) and reliability on MRI (inter-rater: 0.860; intrarater: 0.838) was comparable with the original scale (CT intrarater: 0.750 and on MRI inter-rater: 0.845; intrarater: 0.853). The time required to administer the operationalized scale (4'2″ for MRI and 1'18″ for CT) was similar to that of the original scale (3'56″ for MRI and 1'16″ for CT). The original scale and operationalized scale also significantly correlated with WMC volume (operationalized scale ρ = 0.613, P < 0.001, original scale ρ = 0.638, P < 0.001). CONCLUSION: Operational definitions improve the inter-rater reliability of ARWMC scale on CT, and it correlates with volumetric measurement.

Cerebral microbleeds and quality of life in acute ischemic stroke.

This study evaluated the impact of cerebral microbleeds (CMBs) on the health-related quality of life (HRQoL) in 458 Chinese patients with first or recurrent acute ischemic stroke. HRQoL was assessed with the Short Form-36 (SF-36). Univariate analysis showed the presence of lobar CMBs to be negatively correlated with patients' physical functioning (PF; p < 0.01), social function (SF; p < 0.01), and role-emotional (RE; p < 0.05) scores. Subsequent linear regression analysis revealed lobar CMBs to be independently associated with the PF and SF scores (p < 0.05). The limitations of this study include the exclusion of patients with more severe stroke, the lack of longitudinal assessments, the use of a generic rather than stroke-specific HRQoL scale, and the less than optimal sensitivity of the CMB measurement. The study findings suggest that CMBs have a significant impact on the HRQoL of stroke survivors.

Refractory bulbar and respiratory dysfunction in a young Chinese woman with seronegative, muscle-specific tyrosine kinase antibody-positive myasthenia gravis: response to cyclophosphamide and rituximab treatment.

The use of cyclophosphamide and rituximab for patients with refractory myasthenia gravis has shown promising results. We report on a 31-year-old Chinese woman with acetylcholine receptor antibody-negative and muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis who had refractory bulbar dysfunction and respiratory failure despite immunosuppressive therapy and thymectomy, and partial and sustained responses to cyclophosphamide and rituximab treatment, respectively. Myasthenia crisis was diagnosed when she presented in the third trimester of pregnancy with dysphagia, bilateral ptosis, prominent fatigability, and respiratory failure. She required prolonged intensive care and non-invasive ventilatory support despite several courses of intravenous immunoglobulins and plasmapheresis. Pulse cyclophosphamide 500 mg/m(2) was given monthly for 4 consecutive months with a partial response. Rituximab 500 mg weekly was subsequently given for 4 weeks with a dramatic and sustained response. She remained symptom-free and assumed full maternal care at 1 year. To the authors' knowledge, this is the first report of a Chinese patient with refractory myasthenia gravis who responded to cyclophosphamide and rituximab.

White matter hyperintensities in post-stroke depression: a case control study.

OBJECTIVE: Despite extensive research on post-stroke depression (PSD), the role of white matter hyperintensities (WMHs) in its pathogenesis remains uncertain. The aim of this study was to evaluate the relationship between WMHs and PSD in Chinese patients with first or recurrent stroke. METHODS: A cohort of 994 patients with acute ischaemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. A psychiatrist administered the Structural Clinical Interview for DSM-IV to all patients and made a diagnosis of PSD 3 months after the index stroke. 78 (7.8%) patients had PSD; 78 stroke patients matched according to age and sex but without PSD served as a control group. The severity and location of WMHs were evaluated with MRI. RESULTS: In comparison with the non-PSD group, patients in the PSD group were more likely to have severe deep WMHs (12.8% vs 1.3%; p=0.009). Severe deep WMHs remained an independent predictor of PSD in the multivariate analysis with an OR of 13.8 (p=0.016). CONCLUSION: The results suggest that WMHs may play a role in the development of PSD. The importance of WMHs in the treatment and outcome of PSD warrants further investigation.

Microbleeds and post-stroke emotional lability.

OBJECTIVE: The clinical significance of microbleeds (MBs) in the development of psychiatric conditions following a stroke is unknown. Lesions located in various cortical and subcortical areas are thought to be involved in the pathophysiology of post-stroke emotional lability (PSEL). This study examined the association between PSEL and MBs. METHODS: A total of 519 Chinese patients with acute ischaemic stroke consecutively admitted to the acute stroke unit of a university affiliated regional hospital in Hong Kong were screened for PSEL 3 months after their index stroke. The number and location of MBs were evaluated with MRI. RESULTS: According to Kim's criteria, 74 (14.3%) patients had PSEL. In comparison with the non-PSEL group, patients in the PSEL group were more likely to have MBs in the thalamus as a whole (16.2% vs 6.5%; p = 0.004), its anterior (6.9% vs 2.0%, p = 0.02) and paramedian territories (8.1% vs 3.1%; p = 0.04), and a higher number of MBs in the entire brain (1.7+3.4 vs 1.3+5.0; p = 0.031). MBs in the thalamus remained an independent predictor of PSEL in the multivariate analysis, with an odds ratio of 4.7 (p = 0.002). CONCLUSION: Our results suggest that MBs in the thalamus may play a role in the development of PSEL. The importance of MBs in PSEL and other psychiatric conditions in stroke survivors warrants further investigation.

Frontal lobe atrophy in depression after stroke.

Background. Frontal lobe atrophy (FLA) is associated with late life depression. However, the role that FLA plays in the development of depression after stroke (DAS) remains unknown. This study thus examined the association between FLA and DAS. Methods. A convenience sample of 705 Chinese patients with acute ischemic stroke admitted to the acute stroke unit of a university-affiliated regional hospital in Hong Kong participated in the study. A psychiatrist administered the Structural Clinical Interview for DSM-IV to all patients and made a diagnosis of DAS three months after the index stroke. Results. Eighty-five (12.1%) patients were diagnosed with DAS. In univariate analysis, the DAS patients were more likely to have severe FLA (14.1% versus 5.6%). Severe FLA remained an independent predictor of DAS in multivariate analysis, with an odds ratio of 2.6 (95% confidence intervals = 1.2-5.9). Conclusions. The results suggest that FLA may play a role in the pathogenesis of DAS, which supports the hypothesis that cumulative vascular burden may be important in predicting DAS. Further investigations are needed to clarify the impact of FLA on the clinical presentation, treatment response, and outcome of DAS in stroke survivors.