Multiple Roads to Success: A Latent Class Analysis on Successful Ageing Among Hong Kong Near-Centenarians and Centenarians (NCC).

Notwithstanding the oldest-old cohort being the fastest-growing population in most ageing societies, characterizing successful ageing in adults of advanced age, such as nonagenarians and centenarians, remains challenging. This study investigated the successful ageing subphenotypes using the data from Hong Kong Centenarian Study 2. Between April 2021 and September 2022, 146 family caregivers of community-dwelling older adults aged 95 or above were interviewed by phone. Latent class analysis identified three classes-Overall Frail (46.6%) with poor mobility, cognitive and functional health, Nonambulant (37.0%) but good functional health, and Robust (16.4%) with overall good health-from 11 indicators based on caregivers' reports. Although we found a low prevalence of fulfillment of all indicators of successful ageing, our findings will help care professionals appreciate the heterogeneity underlying partial successful ageing in this vulnerable cohort for segmented and targeted healthy longevity interventions.

Transcranial direct current stimulation over the primary motor cortex improves speech production in post-stroke dysarthric speakers: A randomized pilot study.

PURPOSE: The current study investigated the therapeutic potential of transcranial direct current stimulation (tDCS) on speech intelligibility, speech-related physiological and vocal functions among post-stroke dysarthric patients. METHOD: Nine chronic post-stroke dysarthric patients were randomly assigned to the stimulation or sham group. The stimulation group received 2mA of anodal tDCS over the left inferior primary motor cortex for 15 minutes, while the sham group received 30s of stimulation under the same settings. All the participants received 10 daily 15 minutes of individualized speech therapy targeting their dominant phonological process or phonemes with the greatest difficulty. The outcome measures included (1) perceptual analysis of single words, passage reading and diadochokinetic rate, (2) acoustic analysis of a sustained vowel, and (3) kinematic analysis of rapid syllable repetitions and syllable production in sentence, conducted before and after the treatment. RESULTS: The results revealed that both the stimulation and sham groups had improved perceptual speech intelligibility at the word level, reduced short rushes of speech during passage reading, improved rate during alternating motion rate, AMR-kha1, and improved articulatory kinematics in AMR-tha1 and syllables /tha1/ and /kha1/ production in sentence. Compared to the sham group, the stimulation group showed significant improvement in articulatory kinematics in AMR-kha1 and syllable /kha1/ production in sentence. The findings also showed that anodal stimulation led to reduced shimmer value in sustained vowel /a/ phonation, positive changes in articulatory kinematics in AMR-tha1 and syllables /pha1/ and /kha1/ production in sentence at the post treatment measure. In addition to positive effects on articulatory control, reduced perturbation of voice amplitude documented in the stimulation group post treatment suggests possible tDCS effects on the vocal function. CONCLUSIONS: The current study documented the beneficial effects of anodal tDCS over the primary motor cortex on speech production and suggested that combined tDCS and speech therapy may promote recovery from post-stroke dysarthria.

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio).

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms.

Association between functional status and ocular surface disease among local elderly population in Hong Kong.

Purpose: To evaluate the correlation between ocular surface disease (OSD) and functional status among elderly population over 60 years old in Hong Kong.Methods: Chinese subjects above 60 years old were recruited from the Ophthalmology clinic in Hong Kong West Cluster. Subjects demographic and questionnaires to evaluate the functional status were used to correlate with OSD objectively with clinical examination to assess the meibomian gland dysfunction (MGD), corneal staining, Schirmer's test and tear break-up time (TBUT); and subjectively with ocular surface disease index (OSDI).Results: Twenty-eight patients were recruited, with a mean age of 71.5 ± 6.8 years. There was good correlation between the findings of the two eyes for bilateral measurements. Corneal staining was present in 75% of the subjects, while 92.9% of them had positive MGD grading. TBUT was reduced in 85.7% of the subjects. There is a negative association between MGD grading and Barthel index (r = -0.55, p< .01), indicating worse activities of daily living is related to worse MGD. OSDI is negatively associated with Schirmer's test (r = -0.49, p< .01). A negative correlation is also found between TBUT value and corneal staining (r = -0.58, p< .01).Conclusions: There is a high prevalence of OSD among our subjects. Lower Barthel index (indicating worse Lawton's instrumental activities of daily living) is associated with worse MGD grading. In elderly with poor functional status, care should be taken to manage their OSD.

Is exercise a senolytic medicine? A systematic review.

Cellular senescence, a state of irreversible growth arrest triggered by various stressors, engages in a category of pathological processes, whereby senescent cells accumulate in mitotic tissues. Senolytics as novel medicine against aging and various diseases through the elimination of senescent cells has emerged rapidly in recent years. Exercise is a potent anti-aging and anti-chronic disease medicine, which has shown the capacity to lower the markers of cellular senescence over the past decade. However, whether exercise is a senolytic medicine for aging and various diseases remains unclear. Here, we have conducted a systematic review of the published literature studying the senolytic effects of exercise or physical activity on senescent cells under various states in both human and animal models. Exercise can reduce the markers of senescent cells in healthy humans, while it lowered the markers of senescent cells in obese but not healthy animals. The discrepancy between human and animal studies may be due to the relatively small volume of research and the variations in markers of senescent cells, types of cells/tissues, and health conditions. These findings suggest that exercise has senolytic properties under certain conditions, which warrant further investigations.

1-phenyl 2-thiourea (PTU) activates autophagy in zebrafish embryos.

1-phenyl 2-thiourea (PTU) is a Tyr (tyrosinase) inhibitor that is extensively used to block pigmentation and improve optical transparency in zebrafish (Danio rerio) embryo. Here, we reported a previously undescribed effect of PTU on macroautophagy/autophagy in zebrafish embryos. Upon 0.003% PTU treatment, aberrant autophagosome and autolysosome formation, accumulation of lysosomes, and elevated autophagic flux were observed in various tissues and organs of zebrafish embryos, such as skin, brain, and muscle. Similar to PTU treatment, autophagic activation and lysosomal accumulation were also observed in the somatic tyr mutant zebrafish embryos, which suggest that Tyr inhibition may contribute to PTU-induced autophagic activation. Furthermore, we demonstrated that autophagy contributes to pigmentation inhibition, but is not essential to the PTU-induced pigmentation inhibition. With the involvement of autophagy in a wide range of physiological and pathological processes and the routine use of PTU in zebrafish research of autophagy-related processes, these observations raise a novel concern in autophagy-related studies using PTU-treated zebrafish embryos.Abbreviations: 3-MA: 3-methyladenine; Atg: autophagy-related; BSA: bovine serum albumin; CHT: caudal hematopoietic tissue; CQ: chloroquine; GFP: green fluorescent protein; hpf: hour-post-fertilization; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NGS: normal goat serum; PtdIns3K: class III phosphatidylinositol 3-kinase; PTU: 1-phenyl 2-thiourea; RFP: red fluorescent protein; Sqstm1: sequestosome 1; tyr: tyrosinase.

Factors Associated with Poor Eye Drop Administration Technique and the Role of Patient Education among Hong Kong Elderly Population.

OBJECTIVES: To identify the risk factors for poor eye drop application technique in treatment-naïve subjects and to assess if patient education can benefit these subjects. METHODS: Chinese subjects above 60 years were recruited. Questionnaires, including Barthel index; Lawton's instrumental activities of daily living (ADL); Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight (FRAIL) scale; and Montreal Cognitive Assessment (MoCA), were used to correlate with eye drop application technique (before and after patient education) using Spearman correlation analysis. A multiple linear regression was conducted to determine the predictors of successful administration technique and the improvement of technique after education. RESULTS: The data from 26 subjects (mean age 72) were analyzed. Eye drop instillation technique score improved from 5.42 at baseline to 7.33 after clear instructions. FRAIL score was an independent predictor of baseline score (p=0.003), as well as the improvement after patient education (p=0.012). Age, sex, education level, visual acuity, Barthel index, MoCA, and ADL score were not correlated with eye drop instillation technique, before nor after patient education. DISCUSSION: In patients with poor functional status as reflected by FRAIL score, eye drop application is prone to be ineffective. Education with step-by-step instructions could effectively improve the success of eye drop application.

Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke.

BACKGROUND: This study was performed to determine the clinical correlates and long-term prognostic implications of microbleed burden and location in Chinese patients with ischemic stroke. METHODS AND RESULTS: We recruited 1003 predominantly Chinese patients with ischemic stroke who received magnetic resonance imaging at the University of Hong Kong. We determined the clinical correlates of microbleeds and the long-term risks (3126 patient-years of follow-up) of recurrent ischemic stroke and intracerebral hemorrhage (ICH) by microbleed burden (0 versus 1, 2-4, and ≥5) and location, adjusting for age, sex, and vascular risk factors and stratified by antithrombotic use. Microbleeds were present in 450 of 1003 of the study population (119/450 had ≥5, 187/450 had mixed location). Having ≥5 microbleeds was independently associated with prior antiplatelet and anticoagulant use, whereas microbleeds of mixed location were independently associated with hypertension and prior anticoagulant use (all P<0.05). Microbleed burden was associated with an increased risk of ICH (microbleed burden versus no microbleeds: 1 microbleed: multivariate hazard ratio: 0.59 [95% confidence interval, 0.07-5.05]; 2-4 microbleeds: multivariate hazard ratio: 2.14 [95% confidence interval, 0.50-9.12]; ≥5 microbleeds: multivariate hazard ratio: 9.51 [95% confidence interval, 3.25-27.81]; Ptrend<0.0001), but the relationship of microbleed burden and risk of recurrent ischemic stroke was not significant (Ptrend=0.054). Similar findings were noted in the 862 of 1003 patients treated with antiplatelet agents only (ICH: Ptrend<0.0001; ischemic stroke Ptrend=0.096). Multivariate analysis revealed that, independent of vascular risk factors, antithrombotic use, and other neuroimaging markers of small vessel disease, having ≥5 microbleeds (multivariate hazard ratio: 6.08 [95% confidence interval, 1.11-33.21]; P=0.037) was identified as an independent predictor of subsequent ICH, but neither microbleed burden nor location was predictive of recurrent ischemic stroke risk. CONCLUSIONS: In Chinese patients with ischemic stroke, a high burden of cerebral microbleeds was significantly associated with an increased risk of ICH; however, neither microbleed location nor burden was associated with recurrent ischemic stroke risk.

Depression Moderates the Frailty-Subjective Health Link among Chinese Near Centenarians and Centenarians.

OBJECTIVE: Very old adults may be physically frail, but they do not necessarily experience poor subjective health. The authors hypothesized that the relationship between frailty and subjective health is moderated by depression for very old people. METHODS: In a cross-sectional study, a survey administered was by a face-to-face interview to 129 community-dwelling older adults aged 95-108. Measurements included the five-item FRAIL scale, the Geriatric Depression Scale Short-Form (GDS), and a subjective health rating. Hierarchical multiple regressions were conducted to test the moderation effects, adjusting for age, gender, living arrangement, perceived socioeconomic status, and cognition. RESULTS: The interaction effect between frailty and depression was significant. Inspection of the simple slopes revealed that those who were more depressed had a more negative frailty-subjective health relationship. There was no significant moderation effect for a withdrawal-apathy-vigor dimension of the GDS. CONCLUSION: Our findings suggest a protective psychological mechanism may enable very old adults to maintain an optimistic view of their health despite their increasing physical and functional limitations.

Toward a Comprehensive Model of Frailty: An Emerging Concept From the Hong Kong Centenarian Study.

OBJECTIVES: A better understanding of the essential components of frailty is important for future developments of management strategies. We aimed to assess the incremental validity of a Comprehensive Model of Frailty (CMF) over Frailty Index (FI) in predicting self-rated health and functional dependency amongst near-centenarians and centenarians. DESIGN: Cross-sectional, community-based study. SETTING: Two community-based social and clinical networks. PARTICIPANTS: One hundred twenty-four community-dwelling Chinese near-centenarians and centenarians. MEASUREMENTS: Frailty was first assessed using a 32-item FI (FI-32). Then, a new CMF was constructed by adding 12 items in the psychological, social/family, environmental, and economic domains to the FI-32. Hierarchical multiple regressions explored whether the new CMF provided significant additional predictive power for self-rated health and instrumental activities of daily living (IADL) dependency. RESULTS: Mean age was 97.7 (standard deviation 2.3) years, with a range from 95 to 108, and 74.2% were female. Overall, 16% of our participants were nonfrail, 59% were prefrail, and 25% were frail. Frailty according to FI-32 significantly predicted self-rated health and IADL dependency beyond the effect of age and gender. Inclusion of the new CMF into the regression models provided significant additional predictive power beyond FI-32 on self-rated health, but not IADL dependency. CONCLUSIONS: A CMF should ideally be a multidimensional and multidisciplinary construct including physical, cognitive, functional, psychosocial/family, environmental, and economic factors.