Persons with Alzheimer disease (AD) commonly present with chronic nonmalignant pain, but long-term use of opioids among this population has not been studied previously. Our aim was to investigate the prevalence of long-term (≥180 days) use of opioids for nonmalignant pain and associated factors among community-dwelling persons with AD and to compare the prevalence with a matched cohort without AD. The Medication use and Alzheimer's disease (MEDALZ) cohort was used for this study, comprising all community-dwelling persons diagnosed with AD in Finland during 2005 to 2011 and their matched comparison persons without AD. After exclusion of persons with active cancer treatment, 62,074 persons with and 62,074 persons without AD were included in this study. Data were collected from nationwide registers. Opioids were used by 13,111 persons with and by 16,659 without AD. Overall long-term opioid use was more common among persons without AD (8.7%) than among persons with AD (7.2%, P < 0.0001). However, among opioid users, prevalence of long-term opioid use was slightly higher among persons with AD than among those without AD (34.2% vs 32.3%, respectively, P = 0.0004). Long-term use of transdermal opioids was more than 2-fold among opioid users with AD (13.2%) compared with users without AD (5.5%). Factors associated with long-term opioid use included AD, age ≥80 years, female sex, rheumatoid arthritis, osteoporosis, low socioeconomic position, history of substance abuse, and long-term benzodiazepine use. Prevalence of long-term opioid use was somewhat similar among both groups. Among persons with AD, long-term opioid use was strongly associated with transdermal opioids.

Pain and factors related to it constitute serious health problems in the older population. This populationbased cross-sectional study aimed to investigate whether musculoskeletal pain is associated with mobility limitation and whether the relationship between pain and mobility limitation varies according to the use of analgesics among community-dwelling older people. A total of 622 community-dwelling participants aged 75 years and older (mean age 80.4, 74% women) were interviewed about presence and severity of musculoskeletal pain. Self-reported analgesic drug utilization was verified against medical records. Mobility limitation was assessed by the Timed Up & Go test (TUG) time of >13.5 s or inability to perform the test. Logistic regression was used to evaluate the pain-affect associations, with associations expressed as odds ratios with 95% confidence intervals (CI). After adjustment for several covariates, musculoskeletal pain remained independently associated with mobility limitation (odds ratio = 1.83; 95% CI 1.16, 2.89). The risk of mobility limitation was highest among those who reported severe or moderate pain (1.84; 1.13, 3.13) and among those who used analgesics (2.37; 1.37, 4.11). In conclusion, musculoskeletal pain increases the risk for mobility limitation. The present findings underline the importance of the careful assessment and pharmacological and nonpharmacological management of pain in promoting mobility in older age.

Frailty was associated with a higher prevalence of analgesic use. As frail older people may be more susceptible to adverse events, careful selection of analgesics is warranted. Clinicians should pay more attention to pain management to ensure adequate pain relief.

Chronic musculoskeletal pain is a highly persistent condition among community-dwelling older persons and it is related to poor health and mobility difficulties. In addition, the use of daily analgesic is low despite the continuous nature of chronic pain.

The objective of this study was to investigate whether incident opioid use is associated with an increased risk of hip fractures among community-dwelling persons with Alzheimer disease (AD) and to assess the association in terms of duration of use and opioid strength. Among community-dwelling persons with AD diagnosed in 2010 to 2011 (N = 23,100), a matched cohort study comparing incident opioid users (N = 4750) with opioid nonusers (N = 4750) was constructed. Matching was based on age, sex, and time since AD diagnosis at opioid initiation. Data on drug use and hip fractures were retrieved from nationwide registers. Incident opioid users were identified with a 1-year washout. Cox proportional hazard models compared the risk of hip fracture between opioid use and nonuse, and were weighted with inverse probability of treatment (IPT), based on a propensity score. Age-adjusted incidence rate of hip fractures was 3.47 (95% confidence interval [CI] 2.62-4.33) during opioid use and 1.94 (95% CI 1.65-2.22) during nonuse. Opioid use was associated with an increased risk of hip fracture (IPT-weighted hazard ratio [HR] 1.96, 95% CI 1.27-3.02). The risk was observed during the first 2 months of use (IPT-weighted HR 2.37, 1.04-5.41) and attenuated after that. The results suggest an increase in the risk of hip fracture by increasing opioid strength; weak opioids IPT-weighted HR 1.75 (0.91-3.35), buprenorphine IPT-weighted HR 2.10 (1.41-3.13), and strong opioids IPT-weighted HR 2.89 (1.32-6.32). Further research is needed to find out whether the risk of injurious falls is avoidable by slow titration of opioid doses in the beginning of treatment.

Background: Pneumonia is a common cause for hospitalization and excess mortality among persons with Alzheimer's disease (AD), but little research exists evaluating drug use as its risk factor.Objective: We investigated the association between opioid use and hospital-treated pneumonia among community dwellers with AD.Methods: This study was part of the Medication use and Alzheimer's disease (MEDALZ) cohort. We included all community dwellers newly diagnosed with AD during 2010-2011 in Finland with incident prescription opioid use (n=5,623) and age-, sex-and time since AD diagnosis-matched nonusers (n=5,623). Opioid use data, modelled from pharmacy dispensing data, and hospitaltreated pneumonia were retrieved from nationwide registers. Patients with active cancer treatment were excluded. Hazard models compared opioid users to nonusers, adjusting for comorbidities, socioeconomic position and other drug use.Results: Incident opioid use was associated with an increased risk of hospital-treated pneumonia compared to nonuse (adjusted HR, aHR 1.34, 95% CI 1.14-1.57). Highest risk was observed during the first two months of use (aHR 2.58, 95% CI 1.87-3.55). Compared to weak opioids, buprenorphine was not associated with a higher risk of pneumonia (aHR 1.20, 95% CI 0.83-1.76), but strong opioids were (aHR 1.84, 95% CI 1.15-2.97). The risk was higher for those using ≥50 morphine milligram equivalents (MME)/day (aHR 2.03, 95% CI 1.24-3.31), compared to using <50 MME/day. Conclusions: Opioid use was associated with a risk of hospital-treated pneumonia in a dosedependent manner among persons with AD. Risk-minimization strategies should be considered if opioid therapy is needed.

Pain treatment is important in older adults but may result in adverse events such as falls. Opioids are effective for nociceptive pain but the evidence for neuropathic pain is weak. Nevertheless, both pain and opioids may increase the risk of falls. This narrative literature review aims to summarize the existing knowledge on the opioid-related fall risk in older adults, including the pharmacokinetics and pharmacodynamics, and assist clinicians in prescribing and deprescribing opioids in older persons. We systematically searched relevant literature on opioid-related fall risk in older adults in PubMed and Scopus in December 2020. We reviewed the literature and evaluated fall-related adverse effects of opioids, explaining how to optimally approach deprescribing of opioids in older adults. Opioid use increases fall risk through drowsiness, (orthostatic) hypotension and also through hyponatremia caused by weak opioids. When prescribing, opioids should be started with low dosages if possible, keeping in mind their metabolic genetic variation. Falls are clinically significant adverse effects of all opioids, and the risk may be dose dependent and highest with strong opioids. The risk is most prominent in older adults prone to falls. To reduce the risk of falls, both pain and the need for opioids should be assessed on a regular basis, and deprescribing or changing to a lower dosage or safer alternative should be considered if the clinical condition allows. Deprescribing should be done by reducing the dosage gradually and by assessing and monitoring the pain and withdrawal symptoms at the same time. Weighing the risks and benefits is necessary before prescribing opioids, especially to older persons at high risk of falls. Clinical decision tools assist prescribers in clinical decisions regarding (de-) prescribing.

physicians need to take a more active role in the process of recognising, assessing and controlling persistent pain in older people.