Incident Use of a Potentially Inappropriate Medication and Hip Fracture in Community-Dwelling Older Persons With Alzheimer’s Disease

Background: Potentially inappropriate medications (PIMs) increase the risk of adverse drug reactions and events and have been associated with greater health care service use, such as an increased risk of hospitalization. Objective: The aim of this study is to evaluate the association between PIM use and hip fractures in a nationwide cohort of community-dwelling persons ≥65 years old with Alzheimer’s disease (AD). Methods: The study, which is based on the Finnish nationwide MEDALZ cohort, included all persons diagnosed with AD between 2005 and 2011 (n = 70 718). After a 1-year washout period for PIM use and exclusion of persons with previous hip fracture before AD diagnosis or those who had been hospitalized, we included 47 850 persons ≥65 years old with AD. PIM use was identified using Finnish criteria. Associations between PIM use and hip fracture were analyzed with Cox proportional hazards regression. Results: Of the study population, 12.3% (n = 5895) initiated PIMs during the follow-up (maximum follow-up 2921 days and total number of person-years 139 538.7). Of those, 103 (1.7%) persons had hip fractures during the PIM use period. The results suggest that PIM use was only associated with an increased risk of hip fracture with incident PIM use (adjusted hazard ratio = 1.31; 95% CI = 1.06-1.63; P = 0.014). Conclusions: PIM use is associated with increased risk of hip fracture when a person uses PIMs for the first time. However, the association between PIM use and hip fracture should be investigated more comprehensively in future studies.

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Affective Neuropsychiatric Symptoms as Early Signs of Dementia Risk in Older Adults

Journal of Alzheimer s Disease ◽

10.3233/jad-200190 ◽

2020 ◽

Vol 77 (3) ◽

pp. 1195-1207

Author(s):

Jung Yun Jang ◽

Jean K. Ho ◽

Anna E. Blanken ◽

Shubir Dutt ◽

Daniel A. Nation ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Latent Class ◽

Neuropsychiatric Symptoms ◽

Community Dwelling ◽

Dementia Risk ◽

Increased Risk ◽

Risk Of Progression

Background: Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective: To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods: Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results: Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion: Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.

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The effect of comorbidities on survival in persons with Alzheimer’s disease: a matched cohort study

BMC Geriatrics ◽

10.1186/s12877-021-02130-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Blair Rajamaki ◽

Sirpa Hartikainen ◽

Anna-Maija Tolppanen

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Hip Fracture ◽

Cancer Treatment ◽

Socioeconomic Position ◽

Community Dwelling ◽

Older Age ◽

Risk Of Death

Abstract Background Alzheimer’s disease (AD) is one of the leading causes of death world-wide, but little is known on the role of comorbidities on mortality among people with AD. We studied how comorbidities and age at AD diagnosis impact the survival of people with AD. Methods The Medication Use and Alzheimer’s disease (MEDALZ) cohort study included 70,718 community-dwelling persons in Finland with AD diagnosis from 2005 to 2011 and were matched 1:1 (age, gender, and hospital district) to people without AD (mean age 80 years, 65% women, and the mean follow-up 4.9 and 5.6 years, respectively). Covariates (age, gender, and socioeconomic position), comorbidities (cardiovascular disease, stroke, diabetes, asthma/ chronic obstructive pulmonary disease (COPD), hip fracture, cancer treatment, and mental or behavioral disorders excluding dementia) and survival data were obtained from nationwide registers. Cox proportional hazard models were used to compare risk of death between people with and without AD. Results During the follow-up period a greater proportion of the AD cohort died compared to the non-AD cohort (63% versus 37%). In both cohorts, older age, male gender, lower socioeconomic position, and history of comorbidities were associated with shorter survival and higher risk of death. The associations of comorbidities with survival is weaker in the older age groups and people with AD. Hip fracture (adjusted HR 1.35, 95% CI 1.30–1.41), stroke (1.30, 1.27–1.34), and recent cancer treatment (1.29, 1.26–1.32) had the strongest associations in the AD cohort. Age modified the associations in both cohorts (weaker associations among older people). Conclusion Alzheimer’s disease is the major factor affecting survival, but comorbidities further decrease survival also in individuals with Alzheimer’s disease. Therefore, appropriate management of care of these comorbidities might affect not only survival but also the wellbeing of this vulnerable population.

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Assessing the Progression of Alzheimer’s Disease in Real-World Settings in Three European Countries

Journal of Alzheimer s Disease ◽

10.3233/jad-201172 ◽

2021 ◽

Vol 80 (2) ◽

pp. 749-759

Author(s):

Albert Lladó ◽

Lutz Froelich ◽

Rezaul K. Khandker ◽

Montserrat Roset ◽

Christopher M. Black ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mixed Model ◽

Primary Objective ◽

Community Dwelling ◽

Behavioral Changes ◽

The Uk ◽

State Examination ◽

Study Inclusion

Background: There exists considerable variation in disease progression rates among patients with Alzheimer’s disease (AD). Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. Results: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, ‘not reached’) years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. Conclusion: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.

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Antipsychotic Use and the Risk of Hip Fracture Among Community-Dwelling Persons With Alzheimer’s Disease

The Journal of Clinical Psychiatry ◽

10.4088/jcp.15m10458 ◽

2017 ◽

Vol 78 (3) ◽

pp. e257-e263 ◽

Cited By ~ 14

Author(s):

Marjaana Koponen ◽

Heidi Taipale ◽

Piia Lavikainen ◽

Antti Tanskanen ◽

Jari Tiihonen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hip Fracture ◽

Community Dwelling

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Incidence of head injury and traumatic brain injury among people with Alzheimer’s disease

Journal of Epidemiology & Community Health ◽

10.1136/jech-2018-211960 ◽

2019 ◽

Vol 73 (5) ◽

pp. 451-454 ◽

Cited By ~ 4

Author(s):

Sarianna Ilmaniemi ◽

Heidi Taipale ◽

Antti Tanskanen ◽

Jari Tiihonen ◽

Sirpa Hartikainen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Head Injury ◽

Head Injuries ◽

Community Dwelling ◽

University Hospital ◽

Health Concern ◽

Increased Risk

BackgroundInjuries caused by falling are a major health concern among older population. For older people, falls are the leading cause of head injuries; especially, persons with cognitive disorders have an increased risk of falling.ObjectiveTo compare the incidence of head injury and traumatic brain injury (TBI) among persons with Alzheimer’s disease (AD) with persons without AD.MethodsThis register-based study was conducted on a nationwide cohort, which includes all community-dwelling persons diagnosed with AD in Finland in 2005–2011. Persons with previous head injuries were excluded, leaving 67 172 persons with AD. For each person with AD, a matching person without AD and previous head injury were identified with respect to age, sex and university hospital district. The Cox proportional hazard model and competing risk analyses were used to estimate HR for head injury and TBI.ResultsPersons with AD had 1.34-fold (95% CI 1.29 to 1.40) risk of head injuries and 1.49-fold (95% CI 1.40 to 1.59) risk of TBIs after accounting for competing risks of death and full adjustment by socioeconomic status, drug use and comorbidities.ConclusionPersons with AD are more likely to have a head injury or TBI incident than persons without AD.

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The Impact of a Long-Term Rivastigmine and Donepezil Treatment on All-Cause Mortality in Patients With Alzheimer’s Disease

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317518775044 ◽

2018 ◽

Vol 33 (6) ◽

pp. 385-393 ◽

Cited By ~ 3

Author(s):

Jakub Kazmierski ◽

Chaido Messini-Zachou ◽

Mara Gkioka ◽

Magda Tsolaki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cox Regression ◽

Symptomatic Treatment ◽

Risk Of Death ◽

Increased Risk ◽

Functional Assessments ◽

The Impact

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.

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98 Use of Drgs with Anticholinergic Properties in People Living with Alzheimer’s Disease: Data from NILVAD

Age and Ageing ◽

10.1093/ageing/afz103.58 ◽

2019 ◽

Vol 48 (Supplement_3) ◽

pp. iii17-iii65

Author(s):

Sean P Kennelly ◽

Adam H Dyer ◽

Claire Murphy ◽

Brian Lawlor

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prolonged Exposure ◽

Anatomical Therapeutic Chemical ◽

Community Dwelling ◽

Disease Assessment ◽

Anticholinergic Medication ◽

Dementia Severity ◽

Increased Risk ◽

Anticholinergic Burden

Abstract Background Prolonged exposure to anticholinergic medication, particularly in midlife, is associated with increased risk of cognitive impairment/dementia. Less well explored is the ongoing use of drugs with anticholinergic properties in patients with Alzheimer’s Disease (AD), where the potential to accelerate cognitive decline may be greatest. Methods We analysed medication data from the NILVAD trial, a clinical trial examining the efficacy of Nilvadapine in mild-moderate Alzheimer’s Disease (AD). Drgs were coded based on their Anatomical Therapeutic Chemical (ATC) classification and Anticholinergic Burden Scale (ABS) applied to each participant’s medication list. Logistic and linear regression were used to model predictors of potential anticholinergic medication use/total ABS score. Results Of 510 participants with AD (mean age 72.8 +/-8.3 years; 62% female), just over one-quarter (N = 134, 26.27%) were prescribed a drug with potential/definite anticholinergic properties. Half of these had an anticholinergic burden score of 3 or greater (N = 67, 13.4%). The most frequent definite anticholinergics prescribed included quetiapine (N=27) oxybutynin (N = 22), paroxetine (N=14) and amitriptyline (N=8). Usage did not significantly differ by country or study arm. Overall, 88.43% of patients were prescribed a cholinesterase inhibitor. On multivariate analysis of potential/definite anticholinergic usage, age (p=0.044; OR 1.03, 1.01-1.06), total number of medications (p=0.001, OR 1.3, 1.18-1.41) as well as a greater dementia severity rated using the Alzheimer’s Disease Assessment Scale (ADAS-Cog) (p=0.008; 1.04 1.01-1.07) were associated with likelihood of anticholinergic use. Conclusion Over one-quarter of community-dwelling older patients with AD are prescribed a drug with potential or definite anticholinergic properties. Use of drugs with potential/definite anticholinergic properties were associated with total medication burden in addition to greater dementia severity at baseline. This is particularly pertinent given the deleterious cognitive effects of anticholinergic medication. Further attention to reducing total anticholinergic burden in patients with dementia is warranted.

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Metformin and Risk of Alzheimer’s Disease Among Community-Dwelling People With Diabetes: A National Case-Control Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz234 ◽

2019 ◽

Vol 105 (4) ◽

pp. e963-e972 ◽

Cited By ~ 10

Author(s):

Janet K Sluggett ◽

Marjaana Koponen ◽

J Simon Bell ◽

Heidi Taipale ◽

Antti Tanskanen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Case Control Study ◽

Conditional Logistic Regression ◽

Case Control ◽

Community Dwelling ◽

High Dose ◽

Defined Daily Doses ◽

Increased Risk ◽

Control Study

Abstract Context Type 2 diabetes has been linked with an increased risk of Alzheimer’s disease (AD). Studies on the association between metformin use and AD have reported conflicting results. Objective To investigate whether metformin use modifies the association between diabetes and incident, clinically verified AD. Design Nested case-control study. Setting All community-dwelling people in Finland. Participants Cases were all community-dwelling Finns with AD diagnosed from 2005 to 2011 and with diabetes diagnosed ≥ 3 years before AD (n = 9862). Cases were matched with up to 2 control persons by age, sex, and diabetes duration (n = 19 550). Main outcome measure Cumulative metformin exposure was determined from reimbursed dispensings over a 10- to 16-year period. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to estimate associations, with adjustment for potential confounders. Results A total of 7225 (73.3%) cases and 14528 (74.3%) controls received metformin at least once. Metformin use (ever use) was not associated with incident AD (aOR 0.99; 95% confidence interval [CI], 0.94–1.05). The adjusted odds of AD were lower among people dispensed metformin for ≥ 10 years (aOR 0.85; 95% CI, 0.76–0.95), those dispensed cumulative defined daily doses (DDDs) of < 1825–3650 (aOR 0.91; 95% CI, 0.84–0.98) and > 3650 DDDs (aOR 0.77; 95% CI, 0.67–0.88), and among persons dispensed an average of 2 g metformin daily (aOR 0.89; 95% CI, 0.82–0.96). Conclusion In this large national sample we found no evidence that metformin use increases the risk of AD. Conversely, long-term and high-dose metformin use was associated with a lower risk of incident AD in older people with diabetes.

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