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

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii17-iii65
Author(s):  
Sean P Kennelly ◽  
Adam H Dyer ◽  
Claire Murphy ◽  
Brian Lawlor

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.

2019 ◽  
Vol 75 (5) ◽  
pp. 987-994 ◽  
Author(s):  
Adam H Dyer ◽  
Claire Murphy ◽  
Ricardo Segurado ◽  
Brian Lawlor ◽  
Sean P Kennelly ◽  
...  

Abstract Background Use of anticholinergic medication is associated with an increased risk of cognitive impairment and/or dementia. Despite this, the impact of continuing medication with anticholinergic properties in those diagnosed with Alzheimer’s Disease (AD) is not clear. Methods Analysis of data from NILVAD, an 18-month randomized controlled trial of Nilvadipine in AD. Effects of ongoing Anticholinergic Cognitive Burden (ACB) on cognition (ADAS-Cog: Alzheimer’s Disease Cog Subsection) and dementia severity (CDR-sb: Clinical Dementia Rating – Sum of Boxes/DAD: Disability Assessment for Dementia) over 18 months was evaluated adjusting for important clinical covariates. Results Just over one-quarter (27.90%, n = 142/510) of patients with mild to moderate AD were prescribed a potential/definite anticholinergic. While ACB score was not associated with greater progression on the ADAS-Cog/CDR-sb over time, a higher total ACB predicted greater dementia severity on the DAD, which persisted after robust covariate adjustment (β Coef: −1.53, 95% CI: −2.83 to −0.23, p = .021). There was a significant interaction between APOE ε4 status and ACB score, with carriers experiencing greater progression on both the CDR-Sb (β Coef: 0.36, 95% CI: 0.05–0.67, p = .021) and DAD (β Coef: −3.84, 95% CI: −7.65 to 0.03, p = .049). Conclusions Ongoing use of anticholinergic medication was associated with greater dementia progression on the DAD, but not the CDR-sb. APOE ε 4 carriers may be particularly vulnerable to the effect of ongoing anticholinergic medication on dementia severity, with significant APOE ε 4 x ACB score interactions demonstrated on both the DAD and CDR-sb.


2019 ◽  
Vol 73 (5) ◽  
pp. 451-454 ◽  
Author(s):  
Sarianna Ilmaniemi ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
Sirpa Hartikainen ◽  
...  

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.


2018 ◽  
Vol 34 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Flávia Borges-Machado ◽  
Óscar Ribeiro ◽  
Arnaldina Sampaio ◽  
Inês Marques-Aleixo ◽  
Joana Meireles ◽  
...  

This quasi-experimental, nonrandomized study examined the feasibility and impact of a multicomponent (MT) intervention on 7 community-dwelling individuals diagnosed with probable Alzheimer’s disease (AD) at mild to moderate stage. During 6 months, patients with AD and their caregivers were submitted to a biweekly exercise program, including muscle strengthening, aerobics, balance, and postural exercises. The following tests were used: Senior Fitness Test and Incremental Treadmill Test, Disability Assessment for Dementia Scale, Alzheimer Disease Assessment Scale–Cognitive, and Quality of Life–Alzheimer’s. Attendance and retention mean rates were high (86% and 78%, respectively). No adverse events occurred. Results revealed a significant beneficial effect on cardiorespiratory fitness ( P = .028), upper ( P = .018) and lower ( P = .026) body muscle strength, agility ( P = .018), and ability to perform daily activities ( P = .018). Data suggest that a biweekly MT intervention is feasible to conduct in patients with AD. Findings also suggest a potential positive effect on mitigating cognitive decline and in positively influencing quality of life.


2019 ◽  
Vol 105 (4) ◽  
pp. e963-e972 ◽  
Author(s):  
Janet K Sluggett ◽  
Marjaana Koponen ◽  
J Simon Bell ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
...  

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.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 992-992
Author(s):  
Molly Frank ◽  
Seho Park ◽  
Kathleen Lane ◽  
Alexia Torke ◽  
Mara Schonberg ◽  
...  

Abstract The incidence of Alzheimer’s disease and related dementias (ADRD) and breast cancer increases with age. Despite being one of the most effective ways to diagnose breast cancer early, mammography in ADRD patients comes with an increased risk of treatment complications and false-positive results. Family caregivers are often involved in the decision-making process, and this study evaluates the relationship between dementia severity and caregiver preferences when making decisions about mammography with the patient alone, and with the patient and doctor. We included 181 caregivers from the Decisions about Cancer screening in Alzheimer’s Disease trial, which uses the Dementia Severity Rating Scale (DSRS) to assess dementia severity and a modified Control Preferences Scale (CPS) to assess each caregiver’s preferred decision-making approach. Multinomial logistic regression models evaluated the relationship between DSRS and CPS categories (active, passive, and collaborative), while controlling for the caregivers’ age, sex, race, education, and relationship to patient. Model 1 examined the caregivers’ preferred role with the patient, and it found a significant association between increased dementia severity and preference for a collaborative approach (p<0.001) or passive approach (p<0.05) compared to an active approach. Model 2 did not find a significant association between dementia severity and the caregivers’ preferred role when making decisions with the patient and doctor; however, those with increased age and education were more likely to prefer an active role. The association between dementia severity, caregiver characteristics, and decision-making preferences supports the need for approaches to support ADRD caregivers with medical decision making.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 42-42
Author(s):  
Chih-Ying Cynthia Li ◽  
Brian Downer ◽  
Lin-Na Chou ◽  
Kenneth Ottenbacher ◽  
Kyriakos S Markides ◽  
...  

Abstract Frailty is associated with an increased risk for Alzheimer’s disease and related dementias (ADRD). However, this association has not been investigated in older Mexican Americans; a population that is high-risk for frailty and ADRD. This study investigated the association between frailty and the development of ADRD over 9-year period. We analyzed 860 Mexican Americans ≥76 years old of the Hispanic Established Populations for the Epidemiological Study of the Elderly (Hispanic-EPESE) who have been linked with Medicare claims data. Survey data from Wave 6 (2007/08) was used to categorize participants as frail (either pre-frail or frail) or non-frail according to the Fried phenotype. The main outcome was ADRD diagnosis after Wave 6 interview. ADRD status was determined using the Chronic Conditions Segment of the Master Beneficiary Summary File. We estimated ADRD disease-free probability during 2007-2016 using midpoint of interval data method stratified by frailty status. Mean age of the study sample was 83.2 years (SD=4.4) and 59.3% were female. We found individuals who were frail had less ADRD-free months (46.5; SD= 36.5-52) compared to those who were non-frail (66.0; SD= 47.5-120). Individuals with a score of less than 21 points on the Mini Mental Status Exam had greater risks of ADRD development (Odds Ratio=1.35, 95% CI= 1.05-1.74) compared to their counterpart, after controlling mortality as a competing risk. Our results suggest being pre-frail, frail or cognitively impaired are risk factors for ADRD in community-dwelling older Mexican Americans.


2020 ◽  
Vol 77 (3) ◽  
pp. 1195-1207
Author(s):  
Jung Yun Jang ◽  
Jean K. Ho ◽  
Anna E. Blanken ◽  
Shubir Dutt ◽  
Daniel A. Nation ◽  
...  

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.


2017 ◽  
Vol 44 (5-6) ◽  
pp. 259-265 ◽  
Author(s):  
Hannes Holm ◽  
Katarina Nägga ◽  
Erik D. Nilsson ◽  
Fabrizio Ricci ◽  
Eduardo Cinosi ◽  
...  

Background: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults. Methods: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke. Results: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values. Conclusions: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.


2021 ◽  
Author(s):  
Cassandra Morrison ◽  
Mahsa Dadar ◽  
Neda Shafiee ◽  
Sylvia Villeneuve ◽  
D. Louis Collins ◽  
...  

AbstractBackgroundPeople with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. Inconsistencies may be related to different methods used to define SCD. The current project examined whether four methods of defining SCD (applied to the same sample) results in different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+) and without SCD (SCD-).MethodsMRI scans and questionnaire data for 273 cognitively normal older adults from Alzheimer’s Disease Neuroimaging Initiative were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry only. A previously validated MRI analysis method (SNIPE) was used to measure hippocampal volume and grading. Deformation-based morphometry was performed to examine volume at regions known to be vulnerable to AD. Logistic regressions were completed to determine whether diagnostic method was associated with volume differences between SCD- and SCD+. Linear mixed effects models were performed to examine the relationship between the definitions of SCD and future cognitive decline.ResultsResults varied between the four methods of defining SCD. Left hippocampal grading was lower in SCD+ than SCD-when using the CCI (p=.041) and Worry (p=.021) definitions. The right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.ConclusionThe current findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.


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