Edeltraut Kröger

Omega-3 fatty acids and risk of dementia: the Canadian Study of Health and Aging

BACKGROUND Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against dementia, although epidemiologic studies have yielded inconclusive results. Fish is the main dietary source of n-3 PUFAs and is sometimes contaminated with mercury. This neurotoxicant may modify the association with dementia. OBJECTIVE We evaluated the association of erythrocyte membrane total n-3 PUFAs, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and blood mercury with the incidence of dementia and Alzheimer disease (AD) in the Canadian Study of Health and Aging (CSHA) with adjustment for confounders including apolipoprotein E epsilon4 (APOE epsilon4) status. DESIGN The CSHA is a cohort study of a representative sample of persons aged > or =65 y, conducted from 1991 to 2002. A subsample of 663 nondemented CSHA subjects with a complete clinical examination, blood samples, and follow-up information was eligible for prospective analyses on laboratory measurements. Of these, 149 were incident cases of dementia, including 105 with AD. RESULTS In adjusted Cox regression models with age as the time scale, there were no associations between total n-3 PUFAs, DHA, or EPA and dementia or AD. In contrast, a mercury concentration in the highest quartile was associated with a reduced risk of dementia (hazard ratio: 0.53; 95% CI: 0.33, 0.88). However, significant risk reductions were limited to subjects with concentrations of both n-3 PUFAs and mercury that were above the median. There was no modification of risk by APOE epsilon4 status. CONCLUSIONS No associations between n-3 PUFAs and dementia or AD were found. The results regarding mercury may indicate a spurious association.

Is Complexity of Work Associated with Risk of Dementia? The Canadian Study of Health and Aging

The authors evaluated the association of complexity of work with data, people, and things with the incidence of dementia, Alzheimers disease, and vascular dementia in the Canadian Study of Health and Aging, while adjusting for work-related physical activity. The Canadian Study of Health and Aging is a 10-year population study, from 1991 to 2001, of a representative sample of persons aged 65 years or older. Lifetime job history allowed application of complexity scores and classification of work-related physical activity. Analyses included 3,557 subjects, of whom 400 were incident dementia cases, including 299 with Alzheimers disease and 93 with vascular dementia. In fully adjusted Cox regression models, high complexity of work with people or things reduced risk of dementia (hazard ratios were 0.66 (95% confidence interval: 0.44, 0.98) and 0.72 (95% confidence interval: 0.52, 0.99), respectively) but not Alzheimers disease. For vascular dementia, hazard ratios were 0.36 (95% confidence interval: 0.15, 0.90) for high complexity of work with people and 0.50 (95% confidence interval: 0.25, 1.00) for high complexity of work with things. Subgroup analyses according to median duration (23 years) of principal occupation showed that associations with complexity varied according to duration of employment. High complexity of work appears to be associated with risk of dementia, but effects may vary according to subtype.

Selecting process quality indicators for the integrated care of vulnerable older adults affected by cognitive impairment or dementia

BackgroundThis study aimed at evaluating face and content validity, feasibility and reliability of process quality indicators developed previously in the United States or other countries. The indicators can be used to evaluate care and services for vulnerable older adults affected by cognitive impairment or dementia within an integrated service system in Quebec, Canada.MethodsA total of 33 clinical experts from three major urban centres in Quebec formed a panel representing two medical specialties (family medicine, geriatrics) and seven health or social services specialties (nursing, occupational therapy, psychology, neuropsychology, pharmacy, nutrition, social work), from primary or secondary levels of care, including long-term care. A modified version of the RAND®/University of California at Los Angeles (UCLA) appropriateness method, a two-round Delphi panel, was used to assess face and content validity of process quality indicators. The appropriateness of indicators was evaluated according to a) agreement of the panel with three criteria, defined as a median rating of 7–9 on a nine-point rating scale, and b) agreement among panellists, judged by the statistical measure of the interpercentile range adjusted for symmetry. Feasibility of quality assessment and reliability of appropriate indicators were then evaluated within a pilot study on 29 patients affected by cognitive impairment or dementia. For measurable indicators the inter-observer reliability was calculated with the Kappa statistic.ResultsInitially, 82 indicators for care of vulnerable older adults with cognitive impairment or dementia were submitted to the panellists. Of those, 72 (88%) were accepted after two rounds. Among 29 patients for whom medical files of the preceding two years were evaluated, 63 (88%) of these indicators were considered applicable at least once, for at least one patient. Only 22 indicators were considered applicable at least once for ten or more out of 29 patients. Four indicators could be measured with the help of a validated questionnaire on patient satisfaction. Inter-observer reliability was moderate (Kappa = 0.57).ConclusionA multidisciplinary panel of experts judged a large majority of the initial indicators valid for use in integrated care systems for vulnerable older adults in Quebec, Canada. Most of these indicators can be measured using patient files or patient or caregiver interviews and reliability of assessment from patient-files is moderate.

Association between nutrition and the evolution of multimorbidity: The importance of fruits and vegetables and whole grain products

BACKGROUND & AIMS Multimorbidity is a common health status. The impact of nutrition on the development of multimorbidity remains to be determined. The aim of this study is to determine the association between foods, macronutrients and micronutrients and the evolution of multimorbidity. METHODS Data from 1020 Chinese who participated in the Jiangsu longitudinal Nutrition Study (JIN) were collected in 2002 (baseline) and 2007 (follow-up). Three-day weighted food records and status for 11 chronic diseases was determined using biomedical measures (hypertension, diabetes, hypercholesterolemia and anemia) or self-reports (coronary heart disease, asthma, stroke, cancer, fracture, arthritis and hepatitis). Participants were divided in six categories of stage of evolution of multimorbidity. Association of foods, macronutrients and micronutrients at baseline with stages in the evolution of multimorbidity were determined. Data were adjusted for age, sex, BMI, marital status, sedentary lifestyle, smoking status, annual income, education and energy intake. RESULTS The prevalence of multimorbidity increased from 14% to 34%. A high consumption of fruit and vegetables (p < 0.05) and grain products other than rice and wheat (p < 0.001) were associated with healthier stages in the evolution of multimorbidity. The consumption of grain products other than rice and wheat was highly correlated with dietary fibers (r = 0.77, p < 0.0001), iron (r = 0.46, p < 0.0001), magnesium (r = 0.49, p < 0.0001) and phosphorus (r = 0.57, p < 0.0001) intake which were also associated with healthier stages. CONCLUSION This study provides the first evidence of an association between nutrition and evolution towards multimorbidity. More precisely, greater consumption of fruits and vegetable and whole grain products consumption appear to lower the risk of multimorbidity.

Discontinuation of cholinesterase inhibitor treatment and determinants thereof in the Netherlands: A retrospective cohort study.

Background The Cholinesterase inhibitors (ChEIs) rivastigmine and galantamine have been approved for the treatment of mild to moderate Alzheimer’s disease in the Netherlands. Differences between ChEIs regarding persistence or the use of effeCtive doses in daily Clinical practice have been observed. However, most studies assessing ChEI discontinuation and associated determinants have been Conducted in North America and there is a lack of knowledge about ChEI discontinuation and its determinants in daily Clinical practice in Europe.Objectives To assess ChEI discontinuation in daily practice in the Netherlands and to seek its determinants, including suboptimal utilization.Methods A retrospective cohort study was performed using data from the Dutch PHARMO Record Linkage System. Included patients were aged ≥50 years at first dispensing of a ChEI, had a first dispensing of a ChEI between 1998 and 2008, had a prior medication history of 12 months and had at least one subsequent dispensing of any kind of medication. The proportion of patients who discontinued ChEIs over 3 years was determined. Cox regression was used to assess determinants for early (≤6 months) discontinuation and, separately, for late discontinuation during a subsequent 30-month follow-up among those persisting with treatment for >6 months.Results At 6 months, 30.8% of 3369 study patients had discontinued ChEIs, compared with 59.0% after 3 years. Thirty-five percent of patients taking rivastigmine reached the WHO-defined daily dose compared with 80% taking galantamine. At 6 months, compared with regular-dose rivastigmine, low-dose rivastigmine or low-dose galantamine was associated with an increased risk of early discontinuation, whereas regular-dose galantamine was associated with a decreased risk, as was concurrent use of cardiac medications, drugs for Parkinson’s disease, propulsives, selective serotonin reuptake inhibitors and benzodiazepines. Associations of ChEI type/dose or comedications with discontinuation among patients persisting for >6 months differed somewhat from associations with discontinuation before 6 months.Conclusions Fewer patients taking rivastigmine than those taking galantamine reached recommended doses. Furthermore, patients taking rivastigmine had an increased risk of early discontinuation compared with patients taking galantamine. Adverse effects leading to treatment intolerance and suboptimal utilization may have been contributing factors to these observed differences.

Adverse Drug Reactions Reported With Cholinesterase Inhibitors An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer’s disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer’s disease (donepezil, rivastigmine, and galantamine) and characterize their seriousness as reported by national pharmacovigilance systems to VigiBase, a World Health Organization International Drug Monitoring Program database, between 1998 and 2013. Methods: All ChEI related reports, submitted to VigiBase between 1998 and 2013 from the five continents were extracted. Analyses were carried out for general, serious, and nonserious ADRs. Results: A total of 18 955 reports (43 753 ADRs) from 58 countries were reported: 60.1% in women; mean age 77.4 ± 9.1 years. Most reports originated from Europe (47.6%) and North America (40.4%). Rivastigmine and donepezil were involved in most reports (41.4% each). The most frequently reported ADRs were neuropsychiatric (31.4%), gastrointestinal (15.9%), general (11.9%), and cardiovascular (11.7%) disorders. During the 2006-2013 period, serious ADRs remained more often reported than nonserious ones; the most serious were neuropsychiatric (34.0%), general (14.0%), cardiovascular (12.1%), and gastrointestinal (11.6%) disorders. Medication errors were reported in 2.0% of serious cases. Death occurred in 2.3% of the reports. Conclusions: This international pharmacovigilance study highlights the ADR pattern induced by ChEIs. Neuropsychiatric events were the most frequently reported ADRs. Serious cardiovascular events were frequently reported, suggesting that their significance has probably been previously underestimated. Given the frailty of the patients and the frequent comedications, caution is advised before introducing a ChEI.

Use of Rivastigmine or Galantamine and Risk of Adverse Cardiac Events: A Database Study from the Netherlands

BACKGROUND Two cholinesterase inhibitors (ChEIs), rivastigmine and galantamine, are used to treat Alzheimer disease in the Netherlands. Several adverse cardiac events have been reported for these medications. OBJECTIVE We aimed to assess if the use of ChEIs increased the risk of cardiac events in the Netherlands. METHODS A cohort crossover study of the PHARMO Record Linking System database included patients who initiated ChEIs at age 50 years or older, had at least 1 dispensing of a ChEI drug between 1998 and 2008, a 1-year history in PHARMO, and 1 subsequent dispensing of any medication. Two outcomes were assessed: a first hospitalization for syncope or atrioventricular block. Poisson and Cox regression were used to calculate incidence densities and hazard ratios for cardiac events during periods with ChEI use, compared with periods without ChEI use. RESULTS During the complete observation period of 8.9 years (interquartile range 6.7 to 10.2) there were 132 first hospitalizations for atrioventricular block and 17 first hospitalizations for syncope among 3358 patients. The adjusted incidence densities were significantly increased during ChEI exposure for syncope and atrioventricular block, when compared with the background incidence densities in the roughly 5 years before the last year before ChEI initiation. However, when exposed periods were compared with the unexposed periods 1 year before ChEI initiation and times after exposure, the adjusted hazard ratios remained increased for syncope and atrioventricular block, but increases were not significant anymore. CONCLUSIONS Exposure to ChEIs might increase the risk of adverse cardiac events, but small numbers of cases limit conclusions about the risk in this population and research on larger study samples is needed.

Plasma polychlorinated biphenyl and organochlorine pesticide concentrations in dementia: The Canadian Study of Health and Aging

BACKGROUND Even though polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides are recognized as neurotoxicants, few studies have investigated their associations with dementia. Here, we assess associations of plasma PCB and OC pesticide concentrations with all-cause dementia and Alzheimers disease (AD). METHODS Analyses are based on data from the Canadian Study of Health and Aging, a population-based study of men and women aged 65+ years at baseline. PCB and OC pesticide concentrations were measured in 2023 participants who had complete clinical evaluations and blood samples; 574 had dementia, including 399 cases of AD. Concentrations were log-transformed and used as continuous variables in logistic regression models to assess their individual associations with dementia and AD. RESULTS After adjustment for blood collection period, total plasma lipids, age, sex, education, apolipoprotein E e4 allele (ApoE4), tobacco and alcohol use, rural/urban residence, and comorbidities, elevated plasma PCB concentrations were not associated with increased prevalence of dementia and AD. Elevated concentrations of some OC pesticides and metabolites such as hexachlorobenzene, cis-nonachlor and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane were significantly associated with a reduced prevalence of dementia. A significant reduced prevalence of AD was also observed with elevated hexachlorobenzene concentrations. Other OC pesticides and metabolites were not associated with the prevalence of dementia or AD. No effect modification by sex and ApoE4 was observed for either dementia or AD. CONCLUSIONS Elevated plasma PCB and OC pesticide concentrations were not associated with higher prevalence of all-cause dementia and AD. The possibility of modest reductions in prevalence with specific OC pesticides remains to be further investigated given the cross-sectional design of this study.

Treatment with rivastigmine or galantamine and risk of urinary incontinence: results from a Dutch database study†

Treatment of Alzheimer disease (AD) with cholinesterase inhibitors (ChEIs) may increase the risk of urinary incontinence (UI).

Fish Consumption, Brain Mercury, and Neuropathology in Patients With Alzheimer Disease and Dementia

This Editorial expresses the potential benefits of fatty fish consumption in helping protect older adults from developing Alzheimer disease and other forms of dementia.