A descriptive study of Lewy body dementia with functional imaging support in a Chinese population: a preliminary study.

INTRODUCTION: Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia. There have been limited clinical studies among Chinese patients with Lewy body dementia. This study aimed to review the presenting clinical features and identify risk factors for complications including falls, dysphagia, aspiration pneumonia, pressure sores, and mortality in Chinese patients with Lewy body dementia. We also wished to identify any difference in clinical features of patients with Lewy body dementia with and without an Alzheimer's disease pattern of functional imaging. METHODS: We retrospectively reviewed 23 patients with Lewy body dementia supported by functional imaging. Baseline demographics, presenting clinical and behavioural and psychological symptoms of dementia, functional and cognitive assessment scores, and complications during follow-up were reviewed. Patients with Lewy body dementia were further classified as having an Alzheimer's disease imaging pattern if functional imaging demonstrated bilateral temporoparietal hypometabolism or hypoperfusion with or without precuneus and posterior cingulate gyrus hypometabolism or hypoperfusion. RESULTS: The pre-imaging accuracy of clinical diagnosis was 52%. In 83% of patients, behavioural and psychological symptoms of dementia were evident. Falls, dysphagia, aspiration pneumonia, pressure sores, and death occurred in 70%, 52%, 26%, 26%, and 30% of patients, respectively with corresponding event rates per person-years of 0.32, 0.17, 0.18, 0.08, and 0.10. Patients with aspiration pneumonia compared with those without were more likely to have dysphagia (100% vs 35%; P=0.01). Deceased patients with Lewy body dementia, compared with alive patients, had a higher (median [interquartile range]) presenting Clinical Dementia Rating score (1 [1-2] vs 0.5 [0.5-1.0]; P=0.01), lower mean (± standard deviation) baseline Barthel index (13 ± 7 vs 18 ± 4; P=0.04), and were more likely to be prescribed levodopa (86% vs 31%; P=0.03). Patients with Lewy body dementia with an Alzheimer's disease pattern of functional imaging, compared with those without the pattern, were younger at presentation (mean ± standard deviation, 73 ± 6 vs 80 ± 6 years; P=0.02) and had a lower Mini-Mental State Examination score at 1 year (15 ± 8 vs 22 ± 6; P=0.05). CONCLUSIONS: Falls, dysphagia, aspiration pneumonia, and pressure sores were common among patients with Lewy body dementia. Those with an Alzheimer's disease pattern of functional imaging had a younger age of onset and lower 1-year Mini-Mental State Examination score.

The first case series of Chinese patients in Hong Kong with familial Alzheimer's disease compared with those with biomarker-confirmed sporadic late-onset Alzheimer's disease.

INTRODUCTION: Patients with familial Alzheimer's disease are being increasingly reported in Hong Kong. The objectives of this study were to report the clinical features of these patients, and to compare them with those with biomarker-confirmed sporadic late-onset Alzheimer's disease. METHODS: All symptomatic Chinese patients with familial Alzheimer's disease who attended Queen Mary Hospital, Memory Clinic between January 1998 and December 2016 were included. Information about clinical features, baseline Mini-Mental State Examination score, and presenting cognitive symptoms or atypical clinical features were collected. Their clinical features were compared with those of 12 patients with sporadic late-onset Alzheimer's disease with cerebrospinal fluid biomarker evidence of Alzheimer's disease and 14 patients with late-onset Alzheimer's disease and positive amyloid loading on Pittsburgh compound B imaging. RESULTS: There were three families with familial Alzheimer's disease among whom eight family members were affected. The mean (± standard deviation) age of onset and the Mini-Mental State Examination score were 48.4 ± 7.7 years and 7.9 ± 9.2, respectively. Compared with the sporadic late-onset Alzheimer's disease patients, those with familial Alzheimer's disease had an earlier age of onset and presentation (both P<0.001) and received the correct diagnosis later (median [interquartile range], 7.5 [5.3-14.5] vs 2 [1.0-3.3] years; P<0.001). Patients with familial disease had a lower Mini-Mental State Examination score at presentation than those having late-onset Alzheimer's disease (mean, 7.9 ± 9.2 vs 17.6 ± 7.2; P=0.01). They also had fewer delusions, and less dysphoria and irritability (0% vs 41.7%, 0% vs 50% and 0% vs 54.2%; P=0.04, 0.01 and 0.01, respectively). There was a trend of less frequent amnesia among patients with familial Alzheimer's disease compared with those having late-onset Alzheimer's disease (75% vs 100%; P=0.05). CONCLUSION: Clinical features differ for patients with familial Alzheimer's disease compared with those with late-onset Alzheimer's disease. There is a delay in diagnosis. Promotion of public awareness of familial Alzheimer's disease is much needed.

Impact of (18)FDG PET and (11)C-PIB PET brain imaging on the diagnosis of Alzheimer's disease and other dementias in a regional memory clinic in Hong Kong.

OBJECTIVE: This study investigated the improvement in the accuracy of diagnosis of dementia subtypes among Chinese dementia patients who underwent [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) with or without carbon 11-labelled Pittsburgh compound B ((11)C-PIB). METHODS: This case series was performed in the Memory Clinic at Queen Mary Hospital, Hong Kong. We reviewed 109 subjects (56.9% were female) who received PET with or without (11)C-PIB between January 2007 and December 2014. Data including age, sex, education level, Mini-Mental State Examination score, Clinical Dementia Rating scale score, neuroimaging report, and pre-/post-imaging clinical diagnoses were collected from medical records. The agreement between the initial and post-PET with or without (11)C-PIB dementia diagnosis was analysed by the Cohen's kappa statistics. RESULTS: The overall accuracy of initial clinical diagnosis of dementia subtype was 63.7%, and diagnosis was subsequently changed in 36.3% of subjects following PET with or without (11)C-PIB. The rate of accurate initial clinical diagnosis (compared with the final post-imaging diagnosis) was 81.5%, 44.4%, 14.3%, 28.6%, 55.6% and 0% for Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, other dementia, and mixed dementia, respectively. The agreement between the initial and final post-imaging dementia subtype diagnosis was only fair, with a Cohen's kappa of 0.25 (95% confidence interval, 0.05-0.45). For the 21 subjects who underwent (11)C-PIB PET imaging, 19% (n=4) of those with Alzheimer's disease (PIB positive) were initially diagnosed with non-Alzheimer's disease dementia. CONCLUSIONS: In this study, PET with or without (11)C-PIB brain imaging helped improve the accuracy of diagnosis of dementia subtype in 36% of our patients with underlying Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

A lucky and reversible cause of 'ischaemic bowel'.

An 81-year-old man was admitted with an infective exacerbation of chronic obstructive pulmonary disease. He also had clinical and radiological features suggestive of ileus. On day 6 after admission, he developed generalised abdominal pain. Urgent computed tomography of the abdomen showed presence of portovenous gas and dilated small bowel with pneumatosis intestinalis and whirl sign. Emergency laparotomy was performed, which showed a 7-mm perforated ulcer over the first part of the duodenum and small bowel volvulus. Omental patch repair and reduction of small bowel volvulus were performed. No bowel resection was required. The patient had a favourable outcome. Clinicians should suspect small bowel volvulus as a cause of ischaemic bowel. Presence of portovenous gas and pneumatosis intestinalis are normally considered to be signs of frank ischaemic bowel. The absence of bowel ischaemia at laparotomy in this patient shows that this is not necessarily the case and prompt surgical treatment could potentially save the bowels and lives of these patients.

Strongyloidiasis in a nonagenarian who previously worked in conservancy services.

We report a case of strongyloidiasis in a patient born in Hong Kong and was possibly infected via her prior occupation in conservancy services. She presented with chronic diarrhoea, anorexia, and extensive scratch marks over the lower extremities. Further assessment yielded eosinophilia, intermittent dyspepsia, and an episode of unexplained Clostridium perfringens bacteraemia. She was treated with a course of albendazole. Subsequently, the eosinophilia and diarrhoea subsided.

Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study.

BACKGROUND: Although most epidemiological studies suggest that non-steroidal anti-inflammatory drug use is inversely associated with prostate cancer risk, the magnitude and specificity of this association remain unclear. METHODS: We examined self-reported aspirin and ibuprofen use in relation to prostate cancer risk among 29 450 men ages 55-74 who were initially screened for prostate cancer from 1993 to 2001 in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Men were followed from their first screening exam until 31 December 2009, during which 3575 cases of prostate cancer were identified. RESULTS: After adjusting for potential confounders, the hazard ratios (HRs) of prostate cancer associated with <1 and ≥ 1 pill of aspirin daily were 0.98 (95% confidence interval (CI), 0.90-1.07) and 0.92 (95% CI: 0.85-0.99), respectively, compared with never use (P for trend 0.04). The effect of taking at least one aspirin daily was more pronounced when restricting the analyses to men older than age 65 or men who had a history of cardiovascular-related diseases or arthritis (HR (95% CI); 0.87 (0.78-0.97), 0.89 (0.80-0.99), and 0.88 (0.78-1.00), respectively). The data did not support an association between ibuprofen use and prostate cancer risk. CONCLUSION: Daily aspirin use, but not ibuprofen use, was associated with lower risk of prostate cancer risk.

Plasma amyloid-ß oligomers level is a biomarker for Alzheimer's disease diagnosis.

Amyloid beta (Aß), especially Aß oligomers, is important in Alzheimer's disease (AD) pathogenesis. We studied plasma Aß(40), Aß(42), and Aß oligomers levels in 44 AD patients and 22 non-demented controls. Cognitive functions were assessed by Chinese version of mini-mental state examination (MMSE), Abbreviated Metal Test (AMT), Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog). Plasma Aß monomers and oligomers levels were measured by ELISA. We found that the median plasma Aß(40) and Aß(42) levels were similar between AD and controls, and without significant correlation with cognition. Plasma Aß oligomers level was higher in AD than controls (642.54 ng/ml [range 103.33-2676.93] versus 444.18 ng/ml [range 150.19-1311.18], p=0.047), and negatively correlated with cognition. In multivariate logistic regression analysis, the highest tertile of Aß oligomers levels showed an increased risk of AD than the combined group of middle and lowest tertiles (OR=8.85, p=0.013), after adjustment of gender, age and APOE4 genotype. Increased plasma Aß oligomers level was associated with decreased MMSE and AMT scores (p=0.037, p=0.043, respectively) and increased ADAS-cog score (p=0.036), suggesting negative correlation with cognitive function. We concluded that plasma Aß oligomers level is an useful biomarker for AD diagnosis.

Neuroprotective and anti-inflammatory activities of atorvastatin in a rat chronic constriction injury model.

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-beta, pIkB/IkB, NFkB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.

Alzheimer's disease: early diagnosis and treatment.

With ageing of populations, the worldwide population of persons with dementia will reach over 81 million by 2040, of which the most common cause is Alzheimer's disease. In recent years, there have been major advances in the understanding of its pathogenesis, methods to diagnose it, and treatment. Magnetic resonance brain imaging, cerebrospinal fluid biomarkers, and Pittsburgh compound B and fluorodeoxyglucose positron emission tomography of the brain can facilitate an accurate diagnosis of Alzheimer's disease in its early stage, and diagnose the mild cognitive impairment stage of Alzheimer's disease. At present, only symptomatic but not disease-modifying drug treatments are available. Donepezil, rivastigmine and galantamine are the currently approved cholinesterase inhibitors for the treatment of mild, moderate, and severe Alzheimer's disease. Overall, cholinesterase inhibitors show beneficial effects on cognition, activity of daily living, behaviour, and overall clinical rating. Memantine is another symptomatic treatment for moderate-to-severe Alzheimer's disease patients. It has a small beneficial effect on cognition, activity of daily living, behaviour, and overall clinical rating. Vitamin E has antioxidant properties, and may be used in some Alzheimer's disease patients without vascular risk factors. Concurrent non-pharmacological and psychosocial management of patients and their caregivers have a very important role. Disease-modifying therapies are still under development, whilst immunotherapy may be a viable option in the near future.

Haemophagocytic lymphohistiocytosis: an uncommon clinical presentation of tuberculosis.

Secondary haemophagocytic lymphohistiocytosis is a rare but fatal complication of tuberculosis. We describe two cases, and review the local and international experience on the management of this clinical entity. Prompt treatment with anti-tuberculous drugs forms the cornerstone of therapeutic success.

Effectiveness of Partially Hydrolyzed Guar Gum in Reducing Constipation in Long Term Care Facility Residents: A Randomized Single-Blinded Placebo-Controlled Trial.

OBJECTIVES: To assess the effectiveness of partially hydrolyzed guar gum (PHGG) in improving constipation and reducing the use of laxatives among long term care facility (LTCF) residents. DESIGN: A single-center, prospective, randomized, placebo-controlled, single-blinded parallel-group trial from September 2021 to November 2021. SETTING: Four LTCF in Hong Kong. PARTICIPANTS: Fifty-two LTCF residents with chronic constipation (mean age: 83.9±7.6 years, male 38%). INTERVENTION: 5g PHGG mixed with 200ml water per day for 4 weeks was given to intervention group participants. Control group received 200ml water for 4 weeks. Participants continued their usual as-needed laxative (lactulose, senna or dulcolax) on their own initiative. MEASUREMENTS: Baseline measurements included age, gender, Charlson comorbidity index, Roackwood's Clinical Frailty Scale, body mass index and daily dietary fiber intake. Outcome measures were fecal characteristics assessed by Bristol Stool Form Scale, bowel opening frequency and laxative use frequency at baseline, first, second, third and fourth week of trial. Adverse events were measured. The study was registered on ClinicalTrial.gov; identifier: NCT05037565. RESULTS: There was no significant difference in bowel frequency and stool characteristics between the treatment group and control group. However, there was a significantly lower frequency of lactulose, senna, and total laxative use in the treatment group compared with controls in the third and fourth week. There was no significant difference in adverse effects between the two groups. CONCLUSION: This study showed that daily dietary fibre supplementation by using PHGG for 4 weeks in LTCF residents results in significantly less laxative use than placebo. It may be an effective way to reduce laxative dependence among older people living in LTCFs.

DNA damage phenotype and prostate cancer risk.

The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%) and faster second phase (27% vs. 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles=3.24, 95% CI=0.98-10.66, p-trend=0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals.

Relationship between symptoms of androgen deficiency and psychological factors and quality of life among Chinese men.

Androgen deficiency in the ageing male (ADAM) was proposed to characterize a symptom cluster of decrease in sexual function and strength, dysphoria and osteopenia in ageing men with decreased levels of androgens. Unlike menopause, literature on the topic is scarce and focuses mainly on the physiological aspects of the problem. However, men with ADAM also face a milieu of psychosocial stressors which may adversely affect their mental health. It is pertinent to examine ADAM within a psychological context. This study aims to determine the prevalence of symptoms of ADAM among Chinese men, and to examine their relationship with psychological distress and quality of life. A cross-sectional design was employed with standardized questionnaires to assess symptoms of ADAM and related psychological factors. The ADAM questionnaire, Hospital Anxiety and Depression Scale, Perceived Stress Scale, General Health Questionnaire and Short Form Health Survey-12 were administered to a community sample of 311 Chinese men (aged 40-80) attending a family medicine clinic in Hong Kong. Demographic information was also collected. A total of 87.8% of the sample was screened ADAM positive using the ADAM questionnaire. Age, duration of marriage, occupation, household income and physical health were found to be significantly associated with ADAM status. ADAM positive individuals were found to have higher anxiety and depression scores, higher stress level, higher psychiatric morbidity and poorer physical and mental quality of life compared with their ADAM negative counterparts. Symptoms of ADAM are prevalent among the Chinese. ADAM positivity as measured by the ADAM questionnaire is associated with poorer psychological well-being and quality of life in the ageing population. Further research and clinical attention to the psychological needs of this population is warranted.

Financial abuse in a mentally incapacitated old man.

A mentally incapacitated 82-year-old man with no relatives was managed by a geriatrician-led multidisciplinary team when medical staff realised he was at risk of being exploited. They initiated a series of protective measures including an emergency guardianship application. The Guardianship Board appointed the Director of Social Welfare as his public guardian. This case illustrates that hospital staff should be alert to potential elder abuse to ensure timely protection of potential victims.

Molecular cytogenetic characterization of chromosome 9-derived material in a human thyroid cancer cell line.

The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the eight years following the accident, the average incidence of childhood PTCs (chPTC) increased 70-fold in Belarus, 200-fold in Gomel, 10-fold in the Ukraine and 50-fold in Tschnigov, Kiev, Rovno, Shitomyr and Tscherkassy compared to the rate of about 1 tumor incidence per 106 children per year prior to 1986 (Likhtarev et al., 1995; Sobolev et al., 1997; Jacob et al., 1998). To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed 'BAC-FISH' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.