University of Oklahoma Health Sciences Center

Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study

Author/s:

Bojana Petek, Henrike Häbel, Hong Xu, Marta Villa-Lopez, Irena Kalar, Minh Tuan Hoang, Silvia Maioli, Joana B Pereira, Shayan Mostafaei, Bengt Winblad, Milica Gregoric Kramberger, Maria Eriksdotter, Sara Garcia-Ptacek

Read more about Statins and cognitive decline in patients with Alzheimer's and mixed dementia: a longitudinal registry-based cohort study
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Background
Disturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.

Objective
To explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.

Methods
A longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.

Results
Our cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.

Conclusions
Some patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses

Keywords

alzheimer's disease Cholesterol metabolism Cognitive impairment cohort study HMG-CoA reductase inhibitors statins

Buprenorphine Dose and Time to Discontinuation Among Patients With Opioid Use Disorder in the Era of Fentanyl

Author/s:

Chambers, Laura C., Hallowell, benjamin D., Zullo, Andrew R.

Question: Are higher doses of buprenorphine treatment for opioid use disorder associated with improved retention in treatment when use of fentanyl (vs heroin) is more prevalent?

Findings: In this cohort study of 6499 patients initiating buprenorphine treatment between 2016 and 2020, those prescribed the recommended daily dose (16 mg) were at significantly greater risk of treatment discontinuation within 180 days than those prescribed a higher dose (24 mg).

Meaning: The results of this study suggest that the value of higher buprenorphine doses than currently recommended needs to be considered for improving retention in treatment.

Keywords

cohort study Opiod use disorder fentanyl

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

Author/s:

W. A., Chung, C. P., Murray, K. T., Malow, B. A., Daugherty, J. R., Stein, C. M.

Background: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.

Methods and findings: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.

Conclusions: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

Keywords

opioids Hypnotics cohort study mortality Drug Overdose

Influence of changes in diet quality on unhealthy aging: the Seniors-ENRICA cohort

Author/s:

Ortolá, Rosario, García-Esquinas, Esther, García-Varela, Giselle, Struijkab, Ellen A., Rodríguez-Artalejo, Fernando, Lopez-Garcia, Esther

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Background

Whether adopting a better diet in late life influences the aging process is still uncertain. Thus, we examined the association between changes in diet quality and unhealthy aging.

Methods

Data came from 2042 individuals aged ≥ 60 years recruited in the Seniors-ENRICA cohort in 2008–2010 (wave 0) and followed-up in 2012 (wave 1) and 2015 (wave 2). Diet quality was assessed with the Mediterranean Diet Adherence Screener (MEDAS), the Mediterranean Diet Score (MDS) and the Alternate Healthy Eating Index-2010 (AHEI-2010) at waves 0 and 1. Unhealthy ageing was measured using a 52-item health deficit accumulation index with 4 domains (functional, self-rated health/vitality, mental health, and morbidity/health services use) at each wave. An increase in dietary indices represents a diet improvement, and a lower deficit accumulation index indicates a health improvement.

Results

Compared with participants with a > 1-point decrease in MEDAS or MDS, those with a > 1-point increase showed lower deficit accumulation from wave 0 to wave 2 (multivariate β [95% CI]: –1.49 [− 2.88 to − 0.10], p-trend = 0.04 for MEDAS; and − 2.20 [− 3.56 to − 0.84], p-trend = 0.002 for MDS) and from wave 1 to wave 2 (− 1.34 [− 2.60 to − 0.09], p-trend = 0.04 for MEDAS). Also, participants with a > 5-point increase in AHEI-2010 showed lower deficit accumulation from wave 0 to wave 1 (− 1.15 [− 2.01 to − 0.28], p-trend = 0.009) and from wave 0 to wave 2 (− 1.21 [− 2.31 to − 0.10], p-trend = 0.03) than those with a > 5-point decrease. These results were mostly due to a strong association between improved diet quality and less functional deterioration.

Conclusions

In older adults, adopting a better diet was associated with less deficit accumulation, particularly functional deterioration. Improving dietary habits may delay unhealthy ageing. Our results have clinical relevance since we have observed that the deficit accumulation index decreases an average of 0.74 annually.

Keywords

cohort study dietary patterns aging

cohort study

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