Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer's disease-nested case-control study.

We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer's disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer's disease. INTRODUCTION: To investigate the association between thiazide use and the risk of low-energy fractures (LEF), and hip fracture among community dwellers with Alzheimer's disease (AD). No prior study has evaluated the effect of thiazides on LEF risk of AD patients. METHODS: LEF cases were identified from the MEDALZ study, including all community-dwelling persons diagnosed with AD in Finland 2005-2011. During the follow-up from AD diagnoses until the end of 2015, cases with LEF (N = 10,416) and hip fracture (N = 5578) were identified. LEF cases were matched with up to three controls without LEF, according to time since AD diagnosis, age and gender. Thiazide use identified from the Prescription register data was modeled with PRE2DUP method. Current use was defined in 0-30 days' time window before the fracture/matching date, and duration of current use was assessed. The association between thiazide exposure and LEFs was assessed with conditional logistic regression. RESULTS: Current thiazide use was observed in 10.5% of LEF cases and 12.5% of controls. Current thiazide use was associated with a decreased risk of LEF (adjusted OR [aOR] 0.83, 95% CI 0.77-0.88). In terms of the duration of use, no association was observed with short-term use (< 1 year or 1-3 years), while longer use (> 3 years) was associated with a reduced risk of LEF (aOR 0.77, 95% CI 0.71-0.83) and hip fracture (aOR 0.68, 95% CI 0.60-0.78). CONCLUSIONS: Our study extends the previous knowledge of reduced fracture risk of thiazides to persons with AD, a population with significantly increased background risk of fractures.

The risk of Alzheimer's disease associated with benzodiazepines and related drugs: a nested case-control study.

OBJECTIVE: To assess the association between benzodiazepine and related drug (BZDR) use and risk of Alzheimer's disease (AD) with cumulative consumption and duration of use based models. METHOD: A nationwide nested case-control study of all Finnish community-dwelling persons who received clinically verified AD diagnosis in 2005-2011 (N = 70 719) and their matched controls (N = 282 862). AD diagnosis was based on DSM-IV and NINCDS-ADRDA criteria. BZDR purchases were extracted from the Prescription Register since 1995. The association between BZDR use and AD was assessed using conditional logistic regression with 5-year lag time between exposure and outcome. RESULTS: Benzodiazepine and related drug use was associated with modestly increased risk of AD (adjusted OR 1.06, 95% CI 1.04-1.08). A dose-response relationship was observed with both cumulative consumption and duration. Adjustment for other psychotropics removed the cumulative dose-response relationship by attenuating the ORs in the highest dose category. CONCLUSION: Benzodiazepine and related drug use in general was associated with modestly increased risk of AD. No major differences were observed between different subcategories of BZDRs (i.e. benzodiazepines, Z drugs, short-/medium-acting or long-acting BZDRs). As dose-response relationship abolished after adjustment for other psychotropics, it is possible that the association may partially be due to antidepressants and/or antipsychotics, or concomitant use of these medications.

The association of medications with sedative properties with oral health behaviour in community-dwelling older people.

OBJECTIVES: The objective of this study was to determine whether drugs with sedative properties are related to oral health behaviour-such as frequency of toothbrushing, using toothpaste and dental visits-and oral hygiene, measured by the number of teeth with dental plaque, among community-dwelling older people. METHODS: The study population consisted of 159 community-dwelling, dentate, non-smoking, older people from the Oral Health GeMS study (Geriatric Multidisciplinary Strategy for the Good Care of Older People study). The data were collected by interviews and clinical examinations during 2004-2005. Sedative properties of drugs were assessed using the sedative load (SL) model. Logistic and Poisson regression models were used to estimate odds ratios/relative risks (OR/RR) and 95% confidence intervals (CI). RESULTS: After adjusting for confounding factors, SL associated with infrequent toothbrushing (OR 1.72, CI: 0.61-4.89), toothpaste use less than twice a day (OR 3.34, CI: 1.39-8.12), non-regular dental visits (OR 2.28 CI: 0.91-5.30) and the number of teeth with dental plaque (RR 1.20 CI: 1.04-1.39) compared to participants without a SL. CONCLUSIONS: The results of this study suggest that use of drugs with sedative properties indicates poor oral health behaviour among older people.

Body mass index and periodontal infection in a sample of non-smoking older individuals.

OBJECTIVE: The aim of this study was to investigate the association between BMI and periodontal infection in a sample of non-smoking individuals aged 75 years or older. SUBJECTS AND METHODS: The study sample included 157 non-smoking dentate persons (110 women, 47 men, mean age 80.6 years) belonging to the Geriatric Multidisciplinary Strategy for the Good Care of Older People study in Kuopio, Finland. The data were gathered by interview together with geriatric and oral clinical examination. The outcome variable was the number of teeth with periodontal pockets measuring 4 mm or more in depth. Poisson regression models were used to estimate relative risk (RR) and 95% confidence intervals (CI). RESULTS: After adjustment for confounding factors, the relative risk for the number of teeth with deepened periodontal pockets (≥4 mm) was 0.7 (CI: 0.6-0.9) among those with a BMI 25-29.99 and 1.1 (CI: 0.8-1.4) among those with a BMI ≥30, compared with those having a BMI <25. CONCLUSION: Within the limitations of this study, including small sample size, possibility of confounding and other biases, the results do not provide evidence that elevated body weight would be a risk for periodontal infection among older people.

Salivary flow rate and periodontal infection - a study among subjects aged 75 years or older.

OBJECTIVE: To analyse the relation of stimulated and unstimulated salivary flow rates to periodontal infection in home-dwelling elderly people aged 75 years or older. SUBJECTS AND METHODS: This study was based on a subpopulation of 157 (111 women, 46 men) home-dwelling, dentate, non-smoking elderly people (mean age 79.8, SD 3.6 years) from the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly Study). The data were collected by interview and oral clinical examination. RESULTS: Persons with very low (< 0.7 ml min⁻¹) and low stimulated salivary flow rates (0.7- < 1.0 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR: 0.7, CI: 0.5-0.9 and RR: 0.7, CI: 0.5-0.9, respectively, when compared with those with normal stimulated salivary flow. Persons with a very low unstimulated salivary flow rate (< 0.1 ml min⁻¹) had a decreased likelihood of having teeth with deepened (≥ 4 mm) periodontal pockets, RR 0.8, CI: 0.6-1.0, when compared with subjects with low/normal unstimulated salivary flow. CONCLUSIONS: In a population of dentate, home-dwelling non-smokers, aged 75 years or older, low stimulated and unstimulated salivary flow rates were weakly associated with a decreased likelihood of having teeth with deep periodontal pockets.

Detection of medications associated with Alzheimer's disease using ensemble methods and cooperative game theory.

OBJECTIVE: To study the feasibility of evaluating feature importance with Shapley Values and ensemble methods in the context of pharmacoepidemiology and medication safety. METHODS: We detected medications associated with Alzheimer's disease (AD) by examining the additive feature attribution with combined approach of Gradient Boosting and Shapley Values in the Medication use and Alzheimer's disease (MEDALZ) study, a nested case-control study of 70,719 verified AD cases in Finland. Our methodological approach is to do binary classification using Gradient boosting (an ensemble of weak classifiers) in a supervised learning manner. Then we apply Shapley Values (from cooperative game theory) to analyze how feature combinations affect the classification result. Medication use with a five to one year time-window before AD diagnosis was ascertained from Prescription register. RESULTS: Antipsychotics with low or medium dose, antidepressants with medium to high dose, and cardiovascular medications with medium to high dose were identified as the contributing features for separating cases with AD from controls. Medium to high amount of irregularity in the purchase pattern were an indicating feature for separating AD cases from controls. The similarity of medication purchases between AD cases and controls made the feature evaluation challenging. CONCLUSIONS: The combined approach of Gradient Boosting and feature evaluation with Shapley Values identified features that were consistent with findings from previous hypothesis-driven studies. Additionally, the results from the additive feature attribution identified new candidates for future studies on AD risk factors. Our approach also shows promise for studies based on observational studies, where feature identification and interactions in populations are of interest; and the applicability of using Shapley Values for evaluating feature relevance in pattern recognition tasks.

Utilization of inpatient care before and after hip fracture: a population-based study.

SUMMARY: Evaluation of hospitalizations in a 70+ population showed that hip fractures (HF) were associated with a significant increase in the utilization of inpatient care for a lengthy period. Hospital days attributable to several diagnostic classes still exceeded both prefracture and population levels in the second year after HF. INTRODUCTION: The goal was to assess effects of HF on the inpatient care utilization. METHODS: The study covered HF patients and the 70+general population (26,000) living in Central Finland. Hospitalization data categorized by the ICD-10 main classes were obtained from the nationwide discharge register. RESULTS: In 2002-2003, 498 residents (mean age 82 SD 7, 74.9% women) of the study area sustained HF. Among them, the number of hospital days was 23, 107, and 52 per person-year in the prefracture, first and second postfracture year, respectively. In the 70+ general population, the number was constantly 11 per year. The age- and gender-adjusted rate ratio of hospital days between the two groups was 1.30 (95% CI 1.27 to 1.32), 6.91 (95% CI 6.85 to 7.00), and 3.61 (95% CI 3.55 to 3.67) for the prefracture, first and second postfracture year, respectively. Hospital days due to injuries were more prevalent in the HF group throughout the period. Moreover, excess of days was seen in six other diagnostic classes in the first and in four classes in the second postfracture year. CONCLUSIONS: Hospital days in HF patients still exceeded both the prefracture and population levels in the second year after HF. Days attributable to several other causes than HF itself became also more prevalent indicating that HF can steeply decrease patients' coping capacity and launch a cascade of impairments in the function of different organ systems.

Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older.

This cross-sectional analysis of a population-based cohort investigates the postural changes in blood pressure (BP) and heart rate and assesses the prevalence of orthostatic hypotension (OH) and its associations with the medicines used by an elderly population. The study population (n=1000) was a random sample of persons aged 75 years or older in the City of Kuopio, Finland. In 2004, altogether, 781 persons participated in the study. After the exclusion of persons living in institutional care (n=82) and those without orthostatic test (n=46), the final study population comprised 653 home-dwelling elderly persons. OH was defined as a > or =20 mm Hg drop of systolic BP or a > or =10 mm Hg drop of diastolic BP or both 1 or 3 min after standing up from supine position. Systolic BP dropped for more than half of the home-dwelling elderly when they stood up from a supine to a standing position. The total prevalence of OH was 34% (n=220). No significant gender or age differences were seen. The prevalence of OH was related to the total number of medicines in regular use (P<0.05). OH and postural changes in BP are more common among the home-dwelling elderly than reported in previous studies. The prevalence of OH is related to the number of medicines in regular use. There is an obvious need to measure orthostatic BP of elderly persons, as low BP and OH are important risk factors especially among the frail elderly persons.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Orthostatic Hypotension and Associated Factors among Home Care Clients Aged 75 Years or Older - A Population-Based Study.

OBJECTIVES: The aim of this study was to examine orthostatic hypotension (OH) and associated factors among home care clients aged 75 years or older. DESIGN: Non-randomised controlled study. SETTING AND PARTICIPANTS: The study sample included 244 home care clients aged 75 years or older living in Eastern and Central Finland. MEASUREMENTS: Nurses, nutritionists and pharmacists collected clinical data including orthostatic blood pressure, depressive symptoms (15-item Geriatric Depression Scale GDS-15), nutritional status (Mini Nutritional Assessment MNA), drug use, self-rated health, daily activities (Barthel ADL Index and Lawton and Brody IADL scale) and self-rated ability to walk 400 metres. Comorbidities were based on medical records. RESULTS: The prevalence of OH was 35.7% (n = 87). No association between OH and the number of drugs used or causative drug use and OH was found. In univariate analysis, coronary heart disease, systolic and diastolic blood pressure in a sitting position and lower mean MNA scores were associated with a risk of OH. Multivariate analysis showed that lower mean MNA scores (OR 1.140, 95% CI: 1.014-1.283) appeared to be independently connected to a risk of OH. CONCLUSION: One-third of the home clients had OH and it was associated with lower MNA scores.

Proton pump inhibitor use and risk of hip fractures among community-dwelling persons with Alzheimer's disease-a nested case-control study.

BACKGROUND: Hip fractures are a major health concern among older persons with Alzheimer's disease, who usually use many concomitant drugs for several diseases. Evidence of the association between proton pump inhibitor use and risk of hip fracture is contradictory. AIM: To investigate whether the long-term use of proton pump inhibitor is associated with risk of hip fractures among community-dwelling persons with Alzheimer's disease. METHODS: In this nested case-control study, the nationwide MEDALZ data were utilised. Community-dwelling persons with Alzheimer's disease who encountered incident hip fracture (N = 4818; mean age 84.1) were included as cases. Four controls were matched for each case at the date of hip fracture (N = 19 235; mean age 84.0). The association between hip fracture and duration of current PPI use (ongoing use during 0-30 days before the index date), and cumulative duration of use during 10 years before was investigated with conditional logistic regression. RESULTS: Long-term or cumulative proton pump inhibitor use was not associated with an increased risk of hip fracture. Current proton pump inhibitor use was associated with an increased risk of hip fracture (adjusted OR 1.12, 95% CI 1.03-1.22). The risk was increased in short-term current use (<1 year) (adjusted OR 1.23, 95% CI 1.10-1.37). CONCLUSIONS: The increased risk of hip fracture was evident only in short-term proton pump inhibitor use, but no association was found for long-term or cumulative use. Thus, our findings do not support previous assumptions that long-term proton pump inhibitor use would be associated with an increased risk of hip fractures.

Smoking makes asthma expensive: a register-based study in Finland.

SETTING: Chronic bronchitis and chronic obstructive pulmonary disease (COPD)/emphysema occur frequently among middle-aged and elderly asthma patients who smoke. OBJECTIVE: To test how much this comorbidity increases the use and costs of health services in comparison with asthma alone. DESIGN: A sample of 6000 adults with a clinical diagnosis of asthma was extracted from a nationwide health insurance register for a postal inquiry. Comorbidity and the use of health services were measured using a questionnaire. Data on medication expenses were obtained from the national prescription register. RESULTS: Altogether 4956 individuals replied, of whom 3160 asthma patients aged > or =40 years (response rate 85%) were chosen for this investigation. Asthma patients with COPD/emphysema (12% of the series) accounted for 21% of all doctor consultations, 39% of the total number of hospital in-patient days and 27% of the total expenses, of which one third were medication costs. The mean annual gross expenditure on treatment services and anti-asthma medications was euro754 per patient for those with asthma alone and euro2107 for those with concurrent COPD/emphysema. Current smoking further increased costs among COPD patients. CONCLUSION: To prevent pulmonary comorbidity and the related high costs, cessation of smoking should be an integral part of the treatment provided for asthma patients.

Individually Tailored Dietary Counseling among Old Home Care Clients - Effects on Nutritional Status.

OBJECTIVE: To evaluate the effect of individually tailored dietary counseling on nutritional status among home care clients aged 75 years or older. DESIGN: Non-randomised controlled study. SETTING AND PARTICIPANTS: The study sample consisted of 224 home care clients (≥ 75 years) (intervention group, n = 127; control group, n = 100) who were at protein-energy malnutrition (PEM) or risk of PEM (MNA score <24 and plasma albumin <35 g/L). INTERVENTION: Individually tailored dietary counseling; the persons were instructed to increase their food intake with energy-dense food items, the number of meals they ate and their consumption of energy-, protein- and nutrient-rich snacks for six months. MEASUREMENTS: The Mini Nutritional Assessment (MNA), Body Mass Index (BMI) and plasma albumin were used to determine nutritional status at the baseline and after the six-month intervention. RESULTS: The mean age of the home care clients was 84.3 (SD 5.5) in the intervention group and 84.4 (SD 5.3) in the control group, and 70 percent were women in both groups. After the six-month nutritional intervention, the MNA score increased 2.3 points and plasma albumin 1.6 g/L in the intervention group, against MNA score decreased -0.2 points and plasma albumin -0.1 g/L in the control group. CONCLUSIONS: Individually tailored dietary counseling may improve nutritional status among older home care clients.

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study.

BACKGROUND: Studies investigating psychiatric disorders as Alzheimer's disease (AD) risk factors have yielded heterogeneous findings. Differences in time windows between the exposure and outcome could be one explanation. We examined whether (1) mental and behavioral disorders in general or (2) specific mental and behavioral disorder categories increase the risk of AD and (3) how the width of the time window between the exposure and outcome affects the results. METHODS: A nationwide nested case-control study of all Finnish clinically verified AD cases, alive in 2005 and their age, sex and region of residence matched controls (n of case-control pairs 27,948). History of hospital-treated mental and behavioral disorders was available since 1972. RESULTS: Altogether 6.9% (n=1932) of the AD cases and 6.4% (n=1784) of controls had a history of any mental and behavioral disorder. Having any mental and behavioral disorder (adjusted OR=1.07, 95% CI=1.00-1.16) or depression/other mood disorder (adjusted OR=1.17, 95% CI=1.05-1.30) were associated with higher risk of AD with 5-year time window but not with 10-year time window (adjusted OR, 95% CI 0.99, 0.91-1.08 for any disorder and 1.08, 0.96-1.23 for depression). CONCLUSIONS: The associations between mental and behavioral disorders and AD were modest and dependent on the time window. Therefore, some of the disorders may represent misdiagnosed prodromal symptoms of AD, which underlines the importance of proper differential diagnostics among older persons. These findings also highlight the importance of appropriate time window in psychiatric and neuroepidemiology research.

Differences in analgesic use in community-dwelling persons with and without Alzheimer's disease.

BACKGROUND: There are conflicting findings about analgesic use among persons with cognitive impairment compared to cognitively intact older persons. The objective of our study was to investigate the prevalence of analgesic use in community-dwelling persons with and without Alzheimer's disease (AD), within six months after AD diagnosis and to find out factors associated with the use of analgesics and specific analgesic groups. METHOD: We utilized data from register based MEDALZ (Medication use and Alzheimer's disease) cohort consisting of all community-dwelling persons diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Altogether, 67,215 persons with AD and one comparison person for each case were included. Drug use data were collected from the Prescription Register and comorbidities from Special Reimbursement and Hospital Discharge Registers. RESULTS: Statistically significant (p < 0.001) yet mostly small differences were found for analgesics use: analgesics were used by 34.9% and 33.5% of persons with and without AD, respectively. Paracetamol was the most frequently used analgesic both among persons with (25.0%) and without AD (19.1%). Persons with AD used less frequently NSAIDs (Nonsteroidal Anti-inflammatory Drugs) (13.2% vs. 17.3%) and mild opioids (5.0% vs. 7.1%), while the use of strong opioids was more common in comparison to persons without AD (1.3% vs. 1.1%, respectively). Analgesic users were more likely women, aged ≥80 years, had asthma/COPD, cardiovascular disease, diabetes, cancer, hip fracture, osteoporosis, rheumatoid arthritis, and lower socioeconomic position. CONCLUSION: Further studies are needed to evaluate the adequateness of pain relief in older persons with and without AD. SIGNIFICANCE: Persons with Alzheimer's disease (AD) used more frequently paracetamol and less frequently NSAIDs and mild opioids. A decreasing trend of NSAID use was observed among persons with AD during the study period.

Effects of individual dietary counseling as part of a comprehensive geriatric assessment (CGA) on nutritional status: a population-based intervention study.

BACKGROUND: Nutritional risk is relatively common in community-dwelling older people. OBJECTIVE: To objective of this study was to evaluate the effects of individual dietary counseling as part of a Comprehensive Geriatric Assessment on nutritional status among community-dwelling people aged 75 years or older. METHODS: Data were obtained from a subpopulation of participants in the population-based Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) intervention study in 2004 to 2007. In the present study, the population consist 173 persons at risk of malnutrition in the year 2005 in an intervention (n=84) and control group (n=89). Nutritional status, body weight, body mass index, serum albumin were performed at the beginning of the study and at a two-year follow-up. The nutritional screening was performed using the Mini Nutritional Assessment (MNA) test. RESULTS: A increase in MNA scores (1.8 95% confidence interval [CI]: 0.7 to 2.0) and in serum albumin (0.8 g/L, 95% CI: 0.2 to 0.9 g/L) were a significant difference between the groups. CONCLUSIONS: Nutritional intervention, even dietary counseling without nutritional supplements, may improve nutritional status.

Musculoskeletal pain and use of analgesics in relation to mobility limitation among community-dwelling persons aged 75 years and older.

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.