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

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Blair Rajamaki ◽  
Sirpa Hartikainen ◽  
Anna-Maija Tolppanen

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.

Author(s):  
Sumaira Khalid ◽  
Usha Sambamoorthi ◽  
Kim E. Innes

Accumulating evidence suggests that certain chronic pain conditions may increase risk for incident Alzheimer’s disease and related dementias (ADRD). Rigorous longitudinal research remains relatively sparse, and the relation of overall chronic pain condition burden to ADRD risk remains little studied, as has the potential mediating role of sleep and mood disorders. In this retrospective cohort study, we investigated the association of common non-cancer chronic pain conditions (NCPC) at baseline to subsequent risk for incident ADRD, and assessed the potential mediating effects of mood and sleep disorders, using baseline and 2-year follow-up data using 11 pooled cohorts (2001–2013) drawn from the U.S. Medicare Current Beneficiaries Survey (MCBS). The study sample comprised 16,934 community-dwelling adults aged ≥65 and ADRD-free at baseline. NCPC included: headache, osteoarthritis, joint pain, back or neck pain, and neuropathic pain, ascertained using claims data; incident ADRD (N = 1149) was identified using claims and survey data. NCPC at baseline remained associated with incident ADRD after adjustment for sociodemographics, lifestyle characteristics, medical history, medications, and other factors (adjusted odds ratio (AOR) for any vs. no NCPC = 1.21, 95% confidence interval (CI) = 1.04–1.40; p = 0.003); the strength and magnitude of this association rose significantly with increasing number of diagnosed NCPCs (AOR for 4+ vs. 0 conditions = 1.91, CI = 1.31–2.80, p-trend < 0.00001). Inclusion of sleep disorders and/or depression/anxiety modestly reduced these risk estimates. Sensitivity analyses yielded similar findings. NCPC was significantly and positively associated with incident ADRD; this association may be partially mediated by mood and sleep disorders. Additional prospective studies with longer-term follow-up are warranted to confirm and extend our findings.


2017 ◽  
Vol 51 (9) ◽  
pp. 725-734 ◽  
Author(s):  
Virva Hyttinen ◽  
Heidi Taipale ◽  
Anna-Maija Tolppanen ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
...  

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.


2021 ◽  
Vol 80 (2) ◽  
pp. 749-759
Author(s):  
Albert Lladó ◽  
Lutz Froelich ◽  
Rezaul K. Khandker ◽  
Montserrat Roset ◽  
Christopher M. Black ◽  
...  

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.


Author(s):  
Chau-Ren Jung ◽  
Yu-Ting Lin ◽  
Bing-Fang Hwang

Several studies with animal research associate air pollution in Alzheimer’s disease (AD) neuropathology, but the actual impact of air pollution on the risk of AD is unknown. Here, this study investigates the association between long-term exposure to ozone (O3) and particulate matter (PM) with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5), and newly diagnosed AD in Taiwan. We conducted a cohort study of 95,690 individuals’ age ≥ 65 during 2001–2010. We obtained PM10 and O3 data from Taiwan Environmental Protection Agency during 2000–2010. Since PM2.5 data is only accessible entirely after 2006, we used the mean ratio between PM2.5 and PM10 during 2006–2010 (0.57) to estimate the PM2.5 concentrations from 2000 to 2005. A Cox proportional hazards model was used to evaluate the associations between O3 and PM2.5 at baseline and changes of O3 and PM2.5 during the follow-up period and AD. The adjusted HR for AD was weakly associated with a raised concentration in O3 at baseline per increase of 9.63 ppb (adjusted HR 1.06, 95% confidence interval (CI) 1.00–1.12). Further, we estimated a 211% risk of increase of AD per increase of 10.91 ppb in O3 over the follow-up period (95% CI 2.92–3.33). We found a 138% risk of increase of AD per increase of 4.34 μg/m3 in PM2.5 over the follow-up period (95% CI 2.21–2.56). These findings suggest long-term exposure to O3 and PM2.5 above the current US EPA standards are associated with increased the risk of AD.


2017 ◽  
Vol 78 (3) ◽  
pp. e257-e263 ◽  
Author(s):  
Marjaana Koponen ◽  
Heidi Taipale ◽  
Piia Lavikainen ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
...  

2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki

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.


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.


2021 ◽  
Vol 11 (12) ◽  
pp. 1386
Author(s):  
Young-Suk Kwon ◽  
Jae-Jun Lee ◽  
Sang-Hwa Lee ◽  
Chulho Kim ◽  
Hyunjae Yu ◽  
...  

The incidence of dementia in patients with surgery under neuraxial anesthesia and the possibility of surgery under neuraxial anesthesia as a risk factor for dementia were investigated. We performed a retrospective matched cohort study with nationwide, representative cohort sample data of the Korean National Health Insurance Service in South Korea between 1 January 2003, and 31 December 2004. The participants were divided into control (n = 4488) and neuraxial groups (n = 1122) using propensity score matching. After 9 years of follow-up, the corresponding incidences of dementia were 11.5 and 14.8 cases per 1000 person-years. The risk of dementia in the surgery under neuraxial group was 1.44-fold higher (95% confidence interval [95%CI], 1.17–1.76) than that in the control group. In the subgroup analysis of dementia, the risk of Alzheimer’s disease in those who underwent surgery under neuraxial anesthesia was 1.48-fold higher (95%CI, 1.17–1.87) than that in those who did not undergo surgery under anesthesia. Our findings suggest that patients who underwent surgery under neuraxial anesthesia had a higher risk of dementia and Alzheimer’s disease than those who did not undergo surgery under neuraxial anesthesia.


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