The effect of childcare activities on cognitive status and depression in older adults: gender differences in a 4.4-year longitudinal study.

OBJECTIVES: Although involvement in childcare activities seems to promote better physical and mental health in older adults, its impact on cognitive status and depression has not yet been fully elucidated. We aimed to analyze the association between engagement in childcare activities and cognitive and psychological status over a 4.4-year period in community-dwelling older adults. METHODS: Two thousand one hundred four subjects older than 65 years without severe cognitive impairment at baseline were categorized according to the frequency of their involvement in childcare activities (everyday, occasionally, never). The participants' cognitive status and depressive symptoms were evaluated at baseline and after 4.4 years. RESULTS: During the follow-up, 269 (12.8%) new cases of cognitive impairment and 229 (10.9%) new cases of depression were registered. Men engaged in childcare showed an almost 20% lower risk of cognitive impairment and cognitive decline. Women demonstrated similar results, except for those occasionally involved in childcare, who had a higher risk of cognitive decline compared with women who never engaged in it. The risk of developing depression was reduced in men involved daily (OR = 0.44, 95% CI: 0.30-0.62, p < 0.0001) and occasionally in childcare, who also demonstrated a lower risk of exacerbating depressive symptoms compared with subjects who never involved in it. The onset of depression was reduced in women occasionally engaged in childcare (OR = 0.68, 95% CI: 0.56-0.82, p < 0.0001), but not significantly in those daily involved in it. CONCLUSIONS: Involvement of older adults in childcare activities seems to lower the risk of cognitive impairment in both genders and to prevent onset or worsening of depression particularly in older men. Copyright © 2017 John Wiley & Sons, Ltd.

Monitoring Plasma Levels of Donepezil, 5-O-Desmethyl-Donepezil, 6-O-Desmethyl-Donepezil, and Donepezil-N-Oxide by a Novel HPLC Method in Patients With Alzheimer Disease.

BACKGROUND: In humans, donepezil (D) is metabolized to 5-O-desmethyl-donepezil (5DD), 6-O-desmethyl-donepezil (6DD), and donepezil-N-oxide (DNox). Although 6DD and DNox are pharmacologically active, the activity of 5DD is unknown. At present, no routine methods are available to detect D and its 3 metabolites simultaneously. In this study, a novel high-performance liquid chromatography method was developed and applied to a population of patients with Alzheimer disease on stable treatment with the drug. METHODS: Liquid-liquid extraction from plasma was accomplished by means of a solvent mixture of n-hexane/dichloromethane/ethylacetate (45:40:15) after sample alkalinization. Disopyramide was the internal standard. After evaporation, the residue was reconstituted in 200 µL of mobile phase (acetonitrile 85%:1% acetic acid 15%) and 50 µL was injected into the high-performance liquid chromatography column (X-Terra, RP8; flow: 1 mL/min). Photometric and fluorimetric detectors were used in tandem, to maximize the sensitivity of fluorescent compounds (D, 5DD, and DNox) and also to reveal nonfluorescent compounds (6DD and internal standard). RESULTS: The method was linear in the 10-100 ng/mL concentration range. Imprecision (coefficient of variation) varied between 3.2% and 12.6% and inaccuracy (% mean absolute error) between 1.3% and 13.3%, depending on the compound, concentration, and detection mode. The quantitation limits were 0.1-0.3 ng/mL for fluorescent compounds and 1.2-4.3 ng/mL for photometric compounds. D, 5DD, 6DD, and DNox through concentrations were measured in 54 patients with Alzheimer disease on treatment with D (10 mg q.d.). No interfering peaks by endogenous compounds or coadministered drugs were noted. Plasma concentrations were quite variable among patients (D: 10-106 ng/mL; 5DD: 0.07-2.8 ng/mL; 6DD: 1.2-36 ng/mL; DNox: 0.5-45.4 ng/mL). Of note, in 6 patients, the plasma concentrations of the 2 active metabolites (6DD and DNox) were higher than those of the parent drug. CONCLUSIONS: The above method proved to be suitable for therapeutic drug monitoring and may be useful in ascertaining the real contribution of metabolites to the therapeutic effects of donepezil.