Incidence of and Risk factors for Mild Cognitive Impairment in Chinese Older Adults with Multimorbidity in Hong Kong.

The aim of our study was to identify the incidence rate of and the risk factors for mild cognitive impairment (MCI) among Chinese older adults with multimorbidity in primary care in Hong Kong. Older adults aged 60 years and above with multimorbidity were recruited from the public primary care clinics in Hong Kong. Incidence rates were calculated with the person-years. Cox proportional hazard regression models were used to predict the risk factors for MCI. Sensitivity analysis was performed using multiple imputation. Among 462 participants included in the main analysis, 45 progressed from normal to MCI with an incidence rate of 80.9 cases per 1000 person-years. Older age (HR 2.82, 95% CI 1.26-6.28) and being single (HR 2.15, 95% CI 1.11-4.19) were risk factors for developing MCI in the multivariable regression model. A total of 660 participants were included in the sensitivity analysis, with an MCI incidence of 114.4 cases per 1000 person-years. Older age and being single remained to be risk factors for MCI among older adults with multimorbidity. There may be a high incidence of MCI among Chinese older adults with multimorbidity in primary care in Hong Kong. Future larger studies need to confirm the prevalence and incidence of MCI among primary care Chinese patients.

A pilot feasibility randomized controlled trial on combining mind-body physical exercise, cognitive training, and nurse-led risk factor modification to reduce cognitive decline among older adults with mild cognitive impairment in primary care.

OBJECTIVES: To examine the feasibility and preliminary effectiveness of (1) combining cognitive training, mind-body physical exercise, and nurse-led risk factor modification (CPR), (2) nurse-led risk factor modification (RFM), and (3) health advice (HA) on reducing cognitive decline among older adults with mild cognitive impairment (MCI). METHODS: It was a 3-arm open-labeled pilot randomized controlled trial in the primary care setting in Hong Kong. Nineteen older adults with MCI were randomized to either CPR (n = 6), RFM (n = 7), or HA (n = 6) for 6 months. The primary outcome was the feasibility of the study. Secondary outcomes included the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Montreal Cognitive Assessment Hong Kong version (HK-MoCA), the Clinical Dementia Rating (CDR), the Disability Assessment for Dementia (DAD), quality of life, depression, anxiety, physical activity, health service utilization, and diet. RESULTS: Nineteen out the 98 potential patients were recruited, with a recruitment rate of 19% (95% CI [12-29]%, P = 0.243). The adherence rate of risk factor modification was 89% (95% CI [65-98]%, P = 0.139) for CPR group and 86% (95% CI [63-96]%, P = 0.182) for RFM group. In the CPR group, 53% (95% CI [36-70]%, P = 0.038) of the Tai Chi exercise sessions and 54% (95% CI [37-71]%, P = 0.051) of cognitive sessions were completed. The overall dropout rate was 11% (95% CI [2-34]%, P = 0.456). Significant within group changes were observed in HK-MoCA in RFM (4.50 ± 2.59, P = 0.008), cost of health service utilization in CPR (-4000, quartiles: -6800 to -200, P = 0.043), fish and seafood in HA (-1.10 ± 1.02, P = 0.047), and sugar in HA (2.69 ± 1.80, P = 0.015). Group × time interactions were noted on HK-MoCA favoring the RFM group (P = 0.000), DAD score favoring CPR group (P = 0.027), GAS-20 favoring CPR group (P = 0.026), number of servings of fish and seafood (P = 0.004), and sugar (P < 0.001) ate per day. CONCLUSIONS: In this pilot study, RFM and the multi-domain approach CPR were feasible and had preliminary beneficial effects in older adults with MCI in primary care setting in Hong Kong. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800015324).

The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.

BACKGROUND: Therapeutic vaccination is being studied in eradication and "functional cure" strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP). METHODS: Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels ≤ 200 copies/mL; CD4(+) T-cell counts ≥ 500 cells/mm(3)) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 µg HIV MAG pDNA with 0, 50, 250, or 1000 µg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 µg of IL-12 pDNA by standard IM injection. RESULTS: CD4(+) T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-µg) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). The total increase in the IL-2-expressing CD4 T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P = 0.04). Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo. CONCLUSIONS: HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4(+) but not CD8(+) T-cell responses to multiple HIV-1 antigens.

A randomized controlled trial of palifermin (recombinant human keratinocyte growth factor) for the treatment of inadequate CD4+ T-lymphocyte recovery in patients with HIV-1 infection on antiretroviral therapy.

BACKGROUND: Poor CD4 lymphocyte recovery on antiretroviral therapy (ART) is associated with reduced function of the thymus. Palifermin (keratinocyte growth factor), by providing support to the thymic epithelium, promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease. METHODS: In AIDS Clinical Trials Group A5212, a randomized, double-blind, placebo-controlled study, 99 HIV-infected patients on ART with plasma HIV-1 RNA levels ≤200 copies per milliliter for ≥6 months and CD4 lymphocyte counts <200 cells per cubic milliliter were randomized 1:1:1:1 to receive once daily intravenous administration of placebo or 20, 40, or 60 µg/kg of palifermin on 3 consecutive days. RESULTS: The median change in the CD4 T-cell count from baseline to week 12 was not significantly different between the placebo arm [15 (-16, 23) cells/mm] and the 20-µg/kg dose [11 (2, 32) cells/mm], the 40-µg/kg dose [12 (-2, 25) cells/mm], or the 60-µg/kg dose arm [8 (-13, 35) cells/mm] of palifermin. No significant changes were observed in thymus size or in the number of naive T cells or recent thymic emigrants. CONCLUSIONS: Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART.