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Prescription Medications and Co-Morbidities in Late Middle-Age are Associated with Greater Cognitive Declines: Results from WRAP

ABSTRACT: The present study investigated: 1) sex differences in polypharmacy, comorbidities, self-rated current health (SRH), and cognitive performance, 2) associations between comorbidities, polypharmacy, SRH, and objective measures of health, and 3) associations of these factors with longitudinal cognitive performance. Analyses included 1039 eligible Wisconsin Registry for Alzheimer’s Prevention (WRAP) participants who were cognitively unimpaired at baseline and had ≥2 visits with cognitive composites, self-reported health history, and concurrent medication records. Repeated measures correlation (rmcorr) examined the associations between medications, co-morbidities, SRH, and objective measures of health (including LIfestyle for BRAin Health Index (LIBRA), and depression). Linear mixed-effect models examined associations between medications, co-morbidities, and cognitive change over time using a preclinical Alzheimer’s cognitive composite (PACC3) and cognitive domain z-scores (executive function, working memory, immediate learning, and delayed recall). In secondary analyses, we also examined whether the number of medications interacted with co-morbidities and whether they modified age-related cognitive trajectories. The number of prescribed medications was associated with worse SRH and a higher number of self-reported co-morbidities. More prescribed medications were associated with a faster decline in executive function, and more comorbidities were associated with faster PACC3 decline. Those with a non-elevated number of co-morbidities and medications performed an average of 0.26 SD higher (better) in executive function and an average of 0.18 SD higher on PACC3 than those elevated on both. Associations between medications, co-morbidities, and executive function, and PACC3 suggest that persons with more co-morbidities and medications may be at increased risk of reaching clinical levels of impairment earlier than healthier, less medicated peers.

SUBMITTER: Du L

PROVIDER: S-EPMC9261362 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundA lack of safety data on postpartum medication use presents a potential barrier to breastfeeding and may result in infant exposure to medications in breastmilk. The type and extent of medication use by lactating women requires investigation.MethodsData were collected from the CHILD Cohort Study which enrolled pregnant women across Canada between 2008 and 2012. Participants completed questionnaires regarding medications and non-prescription medications used and breastfeeding status at 3, 6 and 12 months postpartum. Medications, along with self-reported reasons for medication use, were categorized by ontologies [hierarchical controlled vocabulary] as part of a large-scale curation effort to enable more robust investigations of reasons for medication use.ResultsA total of 3542 mother-infant dyads were recruited to the CHILD study. Breastfeeding rates were 87.4%, 75.3%, 45.5% at 3, 6 and 12 months respectively. About 40% of women who were breastfeeding at 3 months used at least one prescription medication during the first three months postpartum; this proportion decreased over time to 29.5% % at 6 months and 32.8% at 12 months. The most commonly used prescription medication by breastfeeding women was domperidone at 3 months (9.0%, n = 229/2540) and 6 months (5.6%, n = 109/1948), and norethisterone at 12 months (4.1%, n = 48/1180). The vast majority of domperidone use by breastfeeding women (97.3%) was for lactation purposes which is off-label (signifying unapproved use of an approved medication). Non-prescription medications were more often used among breastfeeding than non-breastfeeding women (67.6% versus 48.9% at 3 months, p < 0.0001), The most commonly used non-prescription medications were multivitamins and Vitamin D at 3, 6 and 12 months postpartum.ConclusionsIn Canada, medication use is common postpartum; 40% of breastfeeding women use prescription medications in the first 3 months postpartum. A diverse range of medications were used, with many women taking more than one prescription and non-prescription medicines. The most commonly used prescription medication by breastfeeding women were domperidone for off-label lactation support, signalling a need for more data on the efficacy of domperidone for this indication. This data should inform research priorities and communication strategies developed to optimize care during lactation.

Project description:Late-life depression frequently co-occurs with cognitive impairment. To inform clinical management of these conditions, we examined the hypotheses that, relative to cognitively normal elders meeting DSM-IV criteria for major depressive disorder, those with cognitive impairment would require greater intensity of pharmacotherapy to reach criteria for antidepressant response and would take longer to respond.Using data from the MTLD-3 study, we conducted a series of secondary analyses examining the implications of cognitive impairment for short-term, open-trial pharmacotherapy of late-life depression (major depressive disorder in individuals 65 years and older). The treatment algorithm consisted of 3 steps: initial treatment with a selective serotonin reuptake inhibitor (SSRI), a switch to a serotonin-norepinephrine reuptake inhibitor (SNRI) if the patient did not respond, and addition of an atypical antipsychotic if the patient did not respond to the SNRI. The first subject entered the protocol in April 2004, and the last subject exited in September 2009. We examined data for participants who completed the acute phase of MTLD-3 as responders and received a cognitive diagnosis (N = 153) based on National Alzheimer's Coordinating Center (NACC) Uniform Data Set criteria. We divided participants into 3 groups on the basis of NACC cognitive diagnosis: no cognitive disorder (n = 74), mild cognitive impairment (n = 60), and dementia (n = 19). For each group, we calculated the proportion of participants requiring first- (SSRI), second- (SNRI), or third-step (add-on atypical antipsychotic) treatment to meet criteria for response (17-Item Hamilton Depression Rating Scale score ? 10 for 3 consecutive weeks). We compared time to response across groups and correlates of nonresponse.The 3 groups did not differ in intensity of pharmacotherapy (P = .68) or time to response (P = .84). Nonresponse was more strongly correlated with longer major depressive episode duration (P = .0015), presence of recurrent depression (P = .002), and younger current age (P = .047), rather than cognitive status (P = .61).Cognitive status does not appear to impact short-term pharmacotherapy response variability in individuals whose depression responds to treatment with open-trial antidepressants delivered in a supportive, university-based medication clinic.

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Prescription Medications and Co-Morbidities in Late Middle-Age are Associated with Greater Cognitive Declines: Results from WRAP

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