Burden In Older Adults Research Articles

Potentially modifiable factors explaining monozygotic twin discordance in amyloid pathology

AbstractBackgroundThe heritability of global amyloid burden in older adults was previously found to be moderate (41%), suggesting environmental factors to play an important role in early Alzheimer’s disease (AD) pathology. Identifying these factors may aid in the development of successful prevention strategies. Several, potentially modifiable, risk factors for dementia have been previously reported by Livingston and colleagues (Lancet, 2020). We here aim to identify which of these risk factors explain observed twin discordance in amyloid pathology in a sample of cognitively unimpaired monozygotic twin‐pairs.MethodsWe included 31 initially cognitively unimpaired twin‐pairs aged>60 years from the EMIF‐AD PreclinAD study who were discordant on amyloid status (defined by visual read of dynamic [18F]flutemetamol‐PET images). Paired samples t‐tests (continuous measures) and McNemar’s tests (dichotomous measures) were applied to investigate which factors associated with twin discordance. Selected risk factors included comorbid diseases, lifestyle and vascular risk factors (see table 2).ResultsTwins were on average 72.7±7.0 years old, consisted of 48% females, and 58% Apoe‐ε4 carriers (table 1). Twins with a positive amyloid status showed lower body mass index (BMI) and glucose levels compared to their amyloid negative co‐twin (table 2, figure 1A&B). We also observed a trend towards lower diastolic blood pressure in amyloid positive twins (table 2). In accordance with inclusion criteria for the study we observed very low prevalence of comorbid disorders in both groups. Further, no group differences were observed in lifestyle factors, such as smoking, alcohol use, physical activity and sleep quality.ConclusionsIn a sample of monozygotic twin‐pairs discordant for amyloid pathology, we found lower BMI and glucose levels to be associated with the presence of amyloid pathology. Although Livingston and colleagues reported high BMI (obesity) at mid‐life (age 45‐65) to increase the risk for dementia, effects of BMI have previously been found to differ in mid‐ and late‐age populations. In line with our results, lower BMI at later life (>65 years) has previously been found to increase AD‐risk. For the development of prevention strategies, it would be of relevance to further investigate these dynamic age‐related effects.

Association of plasma amyloid-β oligomerization with theta/beta ratio in older adults.

Oligomeric Aβ (OAβ) is a promising candidate marker for Alzheimer's disease (AD) diagnosis. Electroencephalography (EEG) is a potential tool for early detection of AD. Still, whether EEG power ratios, particularly the theta/alpha ratio (TAR) and theta/beta ratio (TBR), reflect Aβ burden-a primary mechanism underlying cognitive impairment and AD. This study investigated the association of TAR and TBR with amyloid burden in older adults based on MDS-OAβ levels. 529 individuals (aged ≥60 years) were recruited. All participants underwent EEG (MINDD SCAN, Ybrain Inc., South Korea) and AlzOn™ test (PeopleBio Inc., Gyeonggi-do, Republic of Korea) for quantifying MDS-OAβ values in the plasma. EEG variables were log-transformed to normalize the data distribution. Using the MDS-OAβ cutoff value (0.78 ng/mL), all participants were classified into two groups: high MDS-OAβ and low MDS-OAβ. Participants with high MDS-OAβ levels had significantly higher TARs and TBRs than those with low MDS-OAβ levels. The log-transformed TBRs in the central lobe (β = 0.161, p = 0.0026), frontal lobe (β = 0.145, p = 0.0044), parietal lobe (β = 0.166, p = 0.0028), occipital lobe (β = 0.158, p = 0.0058), and temporal lobe (beta = 0.162, p = 0.0042) were significantly and positively associated with increases in MDS-OAβ levels. After adjusting for the Bonferroni correction, the TBRs in all lobe regions, except the occipital lobe, were significantly associated with increased MDS-OAβ levels. We found a significant association of MDS-OAβ with TBR in older adults. This finding indicates that an increase in amyloid burden may be associated with an increase in the low-frequency band and a decrease in the relatively high-frequency band.

Changes in Caregiver Burden in Older Adults' Caregivers During the COVID-19 Outbreak.

This study investigated the changes in caregiver burden during the coronavirus disease 2019 (COVID-19) pandemic. The study sample included 827 caregivers for older adults (65+) from the National Health and Aging Trends Study (NHATS) COVID-19 data set. We used paired t-tests to analyze data. The caregivers' assistance in basic and instrumental activities of daily living for care recipients, as well as the amount of time they provided, increased significantly (all ps < .001) during the pandemic compared with before. Approximately, 40% of caregivers reported changes in the amount of assistance they provided during the pandemic. Financial, emotional, and physical difficulties among caregivers have increased, with emotional difficulties being the most frequently reported. The majority of caregivers reported not utilizing any social services during the pandemic. The pandemic may have heightened the caregiver burden. It is important to ensure that caregivers have access to and utilize social services in a physically and psychologically safe manner.

Geriatric assessment-derived deficit accumulation and patient-reported treatment burden in older adults with bladder cancer.

When a person's workload of healthcare exceeds their resources, they experience treatment burden. At the intersection of cancer and aging, little is known about treatment burden. We evaluated the association between a geriatric assessment-derived Deficit Accumulation Index (DAI) and patient-reported treatment burden in older adults with early-stage, non-muscle-invasive bladder cancer (NMIBC). We conducted a cross-sectional survey of older adults with NMIBC (≥65 years). We calculated DAI using the Cancer and Aging Research Group's geriatric assessment and measured urinary symptoms using the Urogenital Distress Inventory-6 (UDI-6). The primary outcome was Treatment Burden Questionnaire (TBQ) score. A negative binomial regression with LASSO penalty was used to model TBQ. We further conducted qualitative thematic content analysis of responses to an open-ended survey question ("What has been your Greatest Challenge in managing medical care for your bladder cancer") and created a joint display with illustrative quotes by DAI category. Among 119 patients, mean age was 78.9 years (SD 7) of whom 56.3% were robust, 30.3% pre-frail, and 13.4% frail. In the multivariable model, DAI and UDI-6 were significantly associated with TBQ. Individuals with DAI above the median (>0.18) had TBQ scores 1.94 times greater than those below (adjusted IRR 1.94, 95% CI 1.33-2.82). Individuals with UDI-6 greater than the median (25) had TBQ scores 1.7 times greater than those below (adjusted IRR 1.70, 95% CI 1.16-2.49). The top 5 themes in the Greatest Challenge question responses were cancer treatments (22.2%), cancer worry (19.2%), urination bother (18.2%), self-management (18.2%), and appointment time (11.1%). DAI and worsening urinary symptoms were associated with higher treatment burden in older adults with NMIBC. These data highlight the need for a holistic approach that reconciles the burden from aging-related conditions with that resulting from cancer treatment.

2 From Bench to Bedside: How Tau Protein is Altered by Perioperative Factors

Objective:Postoperative neurocognitive disorder is common after all forms of surgery in older adults. The mechanisms are multifactorial, and probably require pre-existing neuropathology, whether the patient is symptomatic or not. In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology, one of the neuropathological hallmarks of the disease. Preclinical and human CSF studies suggest that anesthesia and surgery elicits an increment in CNS tauopathy, which may accelerate any preexisting neuropathology and produce a risk of delirium and the commonly reported changes in cognition.Participants and Methods:In this session, the author will present a bench to beside review of how tau protein is altered by perioperative factors and its potential relationship to the impairment of cognition after surgery and anesthesia. Published and ongoing studies will be reviewed to result in a discussion as to why changes in tau protein are concerning in perioperative disorders of cognition.Results:The presenter will initially review pre-clinical studies focusing on the impact of anesthetics and surgery-induced inflammation on tau pathology and how the impairment of resolution of surgery-induced inflammation, notably decreased lipoxin A4 signaling, is altered by aging, gender, or an increase in the tau pathology burden. These preclinical studies have partially informed a multi-center federally funded observational clinical study, currently in progress, involving neuroimaging to determine whether pre-operative CNS tauopathy, as reflected by PET imaging, predicts delirium and other cognitive and functional outcomes. This translational study will also examine whether anesthesia and spine surgery produces a longitudinal change in the brain tau burden in older adults, as compared to control, nonoperative patients.Conclusions:Bench to bedside research is needed in order to promote evidence-based care for patients at risk for ADRD.

Immunogenicity of an AS01-adjuvanted respiratory syncytial virus prefusion F (RSVPreF3) vaccine in animal models

Respiratory syncytial virus (RSV) causes a high disease burden in older adults. An effective vaccine for this RSV-primed population may need to boost/elicit robust RSV-neutralizing antibody responses and recall/induce RSV-specific T cell responses. To inform the selection of the vaccine formulation for older adults, RSVPreF3 (RSV fusion glycoprotein engineered to maintain the prefusion conformation) with/without AS01 adjuvant was evaluated in mice and bovine RSV infection-primed cattle. In mice, RSVPreF3/AS01 elicited robust RSV-A/B-specific neutralization titers and RSV F-specific polyfunctional CD4+ T cell responses exceeding those induced by non-adjuvanted RSVPreF3. In primed bovines, RSVPreF3/AS01 tended to induce higher pre-/post-vaccination fold-increases in RSV-A/B-specific neutralization titers relative to non-adjuvanted and Alum-adjuvanted RSVPreF3 formulations, and elicited higher RSV F-specific CD4+ T cell frequencies relative to the non-adjuvanted vaccine. Though AS01 adjuvanticity varied by animal species and priming status, RSVPreF3/AS01 elicited/boosted RSV-A/B-specific neutralization titers and RSV F-specific CD4+ T cell responses in both animal models, which supported its further clinical evaluation as prophylactic candidate vaccine for older adults.

Tuberculosis and COVID-19 in the elderly: factors driving a higher burden of disease.

Mycobacterium tuberculosis (M.tb) and SARS-CoV-2 are both infections that can lead to severe disease in the lower lung. However, these two infections are caused by very different pathogens (Mycobacterium vs. virus), they have different mechanisms of pathogenesis and immune response, and differ in how long the infection lasts. Despite the differences, SARS-CoV-2 and M.tb share a common feature, which is also frequently observed in other respiratory infections: the burden of disease in the elderly is greater. Here, we discuss possible reasons for the higher burden in older adults, including the effect of co-morbidities, deterioration of the lung environment, auto-immunity, and a reduced antibody response. While the answer is likely to be multifactorial, understanding the main drivers across different infections may allow us to design broader interventions that increase the health-span of older people.

Phenotypes of Symptom, Function, and Medication Burden in Older Adults with Nondialysis Advanced Kidney Disease.

Older adults with advanced chronic kidney disease (CKD, stages 4 and 5) have significant symptoms, polypharmacy, and functional difficulties and prior studies evaluated these burdens separately. Identifying subgroups with similar patterns of burdens could help clinicians optimize care for these individuals. We conducted a secondary analysis of 377 older participants (≥ 70 years old) with stage 4 and 5 CKD at high risk of hospitalization enrolled in a national Veterans Affairs (VA) prospective cohort study. Adults on dialysis or with prior kidney transplant were excluded. We used latent class analysis (LCA) to identify participants with similar patterns across symptoms, medication burden, and function. Sixteen variables were included: symptoms (anxiety, depression, appetite, pain, shortness of breath, fatigue, dizziness, leg weakness, constipation, stiffness using the Symptom Burden Score), polypharmacy (≥ 10 medications and potentially inappropriate medications), and function (activities of daily living (ADL), physical and cognitive instrumental activities of daily living (IADLs), falls in the last year). We also compared 12 month hospitalization and mortality between the three classes. Three classes of participants with similar functional impairment, medication burden, and symptom phenotypes were identified. The largest participant class (N=208) primarily had difficulties with physical IADLs and polypharmacy. The second participant class (N=99) had shortness of breath, constipation, and dizziness. The third participant class (N=70) had complex needs with daily pain, psychological symptoms (anxiety and depression), functional limitations (ADLs and physical and cognitive IADLs), and polypharmacy. The three classes had significantly different levels of comorbidities, financial stress, and social support. There were no significant differences in mortality and hospitalization among the three classes. There are distinct classes of older adults with advanced CKD who have physical and psychological symptoms, functional impairment, and medication burden. Tailoring care for this population should include a multidisciplinary team to address these overlapping symptoms, medication, and functional needs.

Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls. We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults. We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461). Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.

Longitudinal impact of distinct infection trajectories on all-cause mortality of older people in Taiwan: a retrospective, nationwide, population-based study

Infectious diseases are the leading cause of deaths in adults aged 65 years or older. Studies of adverse infection outcomes have been limited to specific infections and acute episodes and have not investigated longitudinal trends of cumulative infections. We aimed to identify distinct trajectories of longitudinal infection episodes in older adults and to assess their corresponding risk of all-cause mortality. In this retrospective cohort study, we included people aged 65 years or older who were admitted to hospital between Jan 1 and Dec 31, 2011, with one of the following infections: urinary tract, pneumonia, sepsis, cellulitis, cholecystitis, peritonitis, endocarditis, and meningitis. Participants were identified from Taiwan's National Health Insurance Research Database. We analysed infection episodes on a quarterly basis during a 5-year period (2011-15) and used group-based trajectory modelling to identify distinct trajectories. We examined the associations between infection trajectories and all-cause mortality using Kaplan-Meier curves and the Cox proportional hazard model. Among 79 666 eligible older adults, we identified four distinct infection trajectories over the 5-year follow-up: infrequent (58 619 [73·6%]), increasing (9746 [12·2%]), decreasing (9069 [11·4%]), and frequent (2232 [2·8%]). Compared with people with infrequent infections, the adjusted hazard ratios for all-cause mortality were 2·96 (95% CI 2·82-3·11) in participants with frequent infections, 2·15 (2·09-2·22) in those with increasing infections, and 1·85 (1·80-1·91) in those with decreasing infections. Older adults with multiple infection episodes, irrespective of type, pathogens, and distinct infection pattern, had greater risk of all-cause mortality compared with those with infrequent infections. Further research to define the overall infection burden in older adults is needed for risk stratification and to inform prevention strategies. The Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education, the National Science and Technology Council, and the Ministry of Science and Technology in Taiwan.

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75years and older.

Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity. Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers. The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

Comparing Use Patterns and Acceptability of Mobile Digital Devices Between Care Recipients and Caregivers.

The use of smartphones and other digital devices (such as tablets and smartwatches) is important for the aging population to enhance and optimize communications with caregivers, families, friends, and providers. It also provides a platform for app-based activities to promote mental, physical, spiritual, and social well-being and virtual social connectedness. We, therefore, examined types of digital devices and categories of smartphone functions used by caregivers and care recipients in comparison to those without any caregiving roles. The project team has developed a smartphone app based on Buddhist meditative practice principles for the enhancement of the physical, mental, cognitive, and emotional well-beingof older adults and their caregiversand tested it in Galveston, Houston, and Dallas, TX. The study comprised a convenient sample of older adults, including members or volunteers of the International Buddhist Progress Society-Dallas (IBPS Dallas) and the University of Texas Medical Branch Osher Lifelong Learning Institute (UTMB OLLI). The survey focused on people who were 55 years and older (n = 219), with 177 valid responses (~80.8%) meeting the study's inclusion criteria. The survey collected data on (1) caregiving role, (2) demographic characteristics and caregiving concerns, and (3) types of devices, functions, and utilization. Descriptive analysis and logistic regression were used to describe and compare patterns of smartphone function/use by the different groups, i.e., caregivers, care recipients, and neither. All of our survey respondents were 55 years and older, and among them, 17.5% were caregivers, 9.1% were care recipients, and 73.4% did not have any role. The majority of the caregivers were females (80.6%), and the average age of their care recipients was 66 years. The care recipients in our sample reported that the average age of their caregiver is only 55 years. Around three-fourths of caregivers reported that they have an app related to health or they are willing to use a health-related app, 32% of them use smart home appliances, whereas only 16% of people who are neither caregivers nor care recipients use such apps. Approximately 42% of caregivers reported taking care of their parents or parents-in-law, and their major concerns are about maintaining their income, scheduling tasks, and updating their knowledge as needed to better care for their loved ones. People use texting or messaging the most. However, the second and third highest utilization are different. The "neither" group significantly spends more time checking email and watching TV; the care recipients spend more time reading and watching TV (sedentary activities); the caregiver group spends more time on phone calls and listening to music. Findings of different patterns of digital device use exist between caregivers, care recipients, and the "neither" group, with 75% of caregivers using a digital device app related to health or reporting willingness to use a health-related app developed from our study. Our findings of their caregiving experiences might alsoinform the design of different intervention programs aimed at promoting mental, physical, and social well-being, improving quality of life while reducing disease/disability burden for older adults, and preventing burnout among caregivers.

Effects of Alzheimer’s disease and related dementias on dental care usage and economic burden in older adults: a cross-sectional study

AimDistinct subtypes of Alzheimer’s disease (AD) and related dementias (RD) might have different effects on dental care usage and economic burden. To determine the effects of AD and RD on...

Frequency and Clinical Impact of Anticholinergic Burden in older patients: Comparing older patients with and without chronic kidney disease

AimThis study aimed to determine the frequency and impact of anticholinergic burden in older adults with chronic kidney disease (CKD) and compare the results to older adults without CKD. MethodAge- and sex-matched older adults (age ≥60) were selected from a total cohort of 1557 subjects, and grouped as CKD (n = 589) and Non-CKD (n = 589). Groups were compared for the frequency, type of anticholinergic agents, and their effects on comprehensive geriatric assessment parameters. The anticholinergic burden was assessed using the anticholinergic burden (ACB) scale. An ACB of ≥2 was categorized as high anticholinergic burden. ResultsThe mean age of the partients was 81±6, and 66% were female. More patients in the CKD group experienced a high anticholinergic burden (45%, versus 38%, p = 0.015). Patients with CKD were more likely to receive beta blocker (25% versus 19%, p = 0.018), diuretic (19% versus 6%, p<0.001), while those who did not have CKD were more likely to be treated with dopaminergic agents (8% versus 12%, p = 0.039). A high anticholinergic burden was associated with sarcopenia (OR 1.62, 95% CI 1.10–2.38, p = 0.015), geriatric depression scale (OR 1.50, 95% CI 1.02–2.20, p = 0.037), and polypharmacy (OR 4.05, 95% CI 2.38–6.90, p<0.001), after adjustment for age, sex and comorbidities in the CKD group (p<0.05). ConclusionOlder patients with CKD are more likely to be exposed to drugs with anticholinergic effects, but have less clinical implications than those without CKD. A high anticholinergic burden is associated with polypharmacy, depression and sarcopenia in CKD.

Polypharmacy and cumulative anticholinergic burden in older adults hospitalized with fall.

Polypharmacy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalized with falls. A noninterventional, prospective cohort study of unselected, acute admissions aged ≥ 65 years. Data were derived from electronic patient health records. Results were analyzed to determine the frequency of polypharmacy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacy, defined as prescription of 5 or more regular oral medications, and ACB score. Four hundred eleven (411) consecutive subjects were included, mean age 83.8 ± 8.0 years: 40.6% men. There were 38.4% patients who were admitted with falls. Incidence of polypharmacy was 80.8%, (88.0% and 76.3% among those admitted with and without fall, respectively). Incidence of ACB score of 0, 1, 2, ≥ 3 was 38.7%, 20.9%, 14.6%, and 25.8%, respectively. On multivariate analysis, age [odds ratio (OR) = 1.030, 95% CI:1.000 ~ 1.050, P = 0.049], ACB score (OR = 1.150, 95% CI:1.020 ~ 1.290, P = 0.025), polypharmacy (OR = 2.140, 95% CI:1.190 ~ 3.870, P = 0.012), but not Charlson Comorbidity Index (OR = 0.920, 95% CI:0.810 ~ 1.040, P = 0.172) were significantly associated with higher falls rate. Of patients admitted with falls, 29.8% had drug-related orthostatic hypotension, 24.7% had drug-related bradycardia, 37.3% were prescribed centrally acting drugs, and 12.0% were taking inappropriate hypoglycemic agents. Polypharmacy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

Anticholinergic burden in older adults with psychiatric illnesses: A cross-sectional study

ObjectivesWe aimed in this study to determine the extent of exposure to anticholinergic drugs in older adults with psychiatric illnesses using the anticholinergic cognitive burden (ACB) scale and to identify the factors associated with anticholinergic drugs use and higher ACB scores. MethodsA cross-sectional study was conducted in the psychogeriatric division of an elderly care hospital. The study sample comprised all inpatients, aged ≥65 years, and diagnosed with psychiatric illness. ResultsAnticholinergic drugs use was reported in 117 (79.6 %) patients, 76 (51.7 %) had an ACB score ≥ 3. Schizophrenia [OR = 5.4 (95 % CI 1.1–10.2), p = 0.02], anemia [OR = 2.2 (95 % CI 1.54–7.89), p = 0.01], and anticholinergic adverse effects [OR = 2.8 (95 % CI 1.12–7.07), p = 0.04] were significantly associated with a higher likelihood of using anticholinergic drugs. The odds of having an ACB score ≥ 3 over an ACB score = 0 were significantly increased by schizophrenia [OR = 4.9 (95 % CI 1.65–8.02), p = 0.01], anemia [OR = 1.32 (95 % CI 1.90–6.90), p = 0.02], and polypharmacy [OR = 1.74 (95 % CI 1.10–2.40), p = 0.04], while they were significantly decreased by age [OR = 0.86 (95 % CI 0.78–0.96), p < 0.001]. Patients with cognitive impairment were less likely than those without cognitive impairment to have an ACB score ≥ 3 over an ACB score = 0. ConclusionsOur study revealed that older adults with psychiatric illnesses were exposed to high anticholinergic burden.

Adjusting for Case Under-Ascertainment in Estimating RSV Hospitalisation Burden of Older Adults in High-Income Countries: a Systematic Review and Modelling Study.

Previous studies suggest diagnostic testing characteristics (i.e. variations in clinical specimens and diagnostic tests) can contribute to underestimation of RSV disease burden. We aimed to improve the understanding of RSV hospitalisation burden in older adults (aged ≥ 65years) in high-income countries through adjusting for case under-ascertainment. We conducted a systematic review to include data on RSV-associated acute respiratory infection (ARI) hospitalisation burden in older adults in high-income countries. To adjust for case under-ascertainment, we developed a two-step framework that incorporated empirical data on the RSV detection proportion of different clinical specimens and testing approaches as well as their statistical uncertainty. We estimated the unadjusted and adjusted RSV-associated hospitalisation burden through multilevel random-effects meta-analysis. We further explored RSV-associated in-hospital mortality burden. We included 12 studies with eligible RSV hospitalisation burden data. We estimated that pooled unadjusted hospitalisation rate was 157 per 100,000 (95%CI 98-252) for adults aged ≥ 65years; the rate was adjusted to 347 per 100,000 (203-595) after accounting for under-ascertainment. The adjusted rate could be translated into 787,000 (460,000-1,347,000) RSV-associated hospitalisations in high-income countries in 2019, which was about 2.2 times the unadjusted estimate. Stratified analysis by age group showed that the adjusted rate increased with age, from 231 per 100,000 in adults aged 65-74years to 692 per 100,000 in adults aged > 85years. The in-hospital case fatality ratio of RSV was 6.1% (3.3-11.0) and the total RSV-associated in-hospital deaths in high-income countries in 2019 could be between 22,000 and 47,000. This study improves the understanding of RSV-associated hospitalisation burden in older adults and shows that the true RSV-associated hospitalisation burden could be 2.2 times what was reported in existing studies. This study has implications for calculating the benefit of interventions to treat and prevent RSV-associated disease.

Drug Burden Index in Older Adults with Psychiatric Illnesses: A Cross-Sectional Study.

Medications with anticholinergic and/or sedative properties are commonly used in the management of psychiatric illnesses. The burden of anticholinergic and sedative medication use has been measured by the Drug Burden Index (DBI) score tool. A higher DBI score has been associated with increased risk of falls, bone and hip fractures, and functional and cognitive impairment, among other serious health outcomes, especially in older adults. We aimed to describe the drug burden in older adults with psychiatric illnesses using DBI, determine the factors that are associated with the drug burden measured by DBI, and examine the association between DBI score and Katz for activities of daily living (ADL) index. A cross-sectional study was conducted in the psychogeriatric division of an aged-care home. The study sample comprised all inpatients, aged ≥ 65 years, diagnosed with psychiatric illness. The data obtained included demographic characteristics, duration of hospital stay, primary psychiatric diagnosis and comorbidities, functional status using the Katz ADL index, and cognitive status using the Mini-Mental State Examination (MMSE) score. DBI score was calculated for each anticholinergic and sedative medication used. Of the 200 patients eligible for analysis, 106 (53.1%) were females and the mean age was 76 ± 9 years. The most commonly encountered chronic disorders were hypertension 102 (51%) and schizophrenia 94 (47%). The use of drugs with anticholinergic and/or sedative effects was seen in 163 (81.5%) patients; the mean DBI score was 1.25 ± 1. The results of the multinomial logistic regression showed that schizophrenia (odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.57-4.45), p = 0.01), level of dependency (OR = 3.50 (95% CI 1.38-5.70), p = 0.001), and polypharmacy (OR = 2.99 (95% CI 2.15-4.29), p = 0.003) were significantly associated with DBI score ≥ 1 compared to DBI score 0. The study showed that anticholinergic and sedative medication exposure measured by DBI was associated with higher levels of dependency on the Katz ADL index in a sample of older adults with psychiatric illnesses from an aged-care home.

Is late-life depression associated with Alzheimer's disease? Evidence from epidemiological, neuropsychological, and neuroimaging perspectives

In 2021, the FDA approved Aducanumab (Aduhelm™), an anti-amyloid antibody intravenous (IV) infusion therapy approved for Alzheimer's disease (AD) that is the first treatment shown to ameliorate neuropathological changes due to AD in the brain. It is well-established that depression increases the risk of future cognitive decline and dementia, but whether depression is specifically associated with AD is unclear, because many of the earlier epidemiological studies employed a relatively short interval (< 5 years) between observation of depression and AD diagnosis. Since neuropathological changes in the brain due to AD may occur years prior to onset of clinical memory symptoms and AD diagnosis, depression that begins late in life may thus represent a non-cognitive prodromal feature of AD. Moreover, the association between depression in older adults and AD biomarkers is also unclear, with some studies suggesting that amyloid-beta, one of the main neuropathological hallmarks of AD, may be reduced in older adults with depression. With the availability of a disease-altering treatment for AD and knowledge that the neuropathological process for AD begins years before onset of clinical memory symptoms, a logical next step in the near future will be to examine whether anti-amyloid therapies can prevent development of AD in high-risk populations. Thus, it is timely to clarify the relationship between depression and dementia. Specifically, is depression an independent risk factor for AD, or is depression associated with dementia more generally? What is the evidence for a distinct form of dementia subtype due to depression?This symposium will address the question of whether major depressive disorder is an independent risk factor for dementia due to AD or other dementia subtypes by presenting evidence from the epidemiological, neuropsychological, and neuroimaging literature. Dr. Linda Mah will begin by presenting an overview of the epidemiological data on the association between depression and AD or dementia subtypes, focusing on differences in the strength of the association as a function of measurement of exposure, follow-up interval, and dementia subtype outcome. Dr. Scott Mackin will present recent work comparing neuropsychological and neuroimaging data including cortico-limbic volume and amyloid-beta burden in older adults with depression versus non-depressed older adults, which provides evidence for late-life depression as having distinct neurodegenerative features independent of AD. Dr. Jennifer Gatchel will present results from a multi-modal neuroimaging study in non-demented older adults with major depressive disorder, which demonstrates a relationship between tau pathology and depression symptoms and decreased interest-motivation-drive, while in contrast, mood symptoms were not associated with either amyloid-beta or medial temporal lobe atrophy. Dr. Benoit Mulsant will serve as discussant for the symposium. Drawing upon the PACt-MD study (“Preventing Alzheimer's dementia with cognitive remediation plus transcranial direct current stimulation in mild cognitive impairment and depression”), Dr. Mulsant will highlight some of the baseline AD biomarker data in the remitted major depressive disorder + mild cognitive impairment group, which suggest that this phenotype may be associated with a distinct dementia subtype. Implications for the clinical management of late-life depression and future research priorities will be discussed.

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein.

Respiratory syncytial virus (RSV) is a common cause of paediatric respiratory tract infection and causes a significant health burden in older adults. Natural immunity to RSV is incomplete, permitting recurrent symptomatic infection over an individual's lifespan. When combined with immunosenescence, this increases older adults' susceptibility to more severe disease symptoms. As RSV prophylaxis is currently limited to infants, older adults represent an important target population for RSV vaccine development. The relationship between RSV and our immune systems is complex, and these interactions require deeper understanding to tailor an effective vaccine candidate towards older adults. To date, vaccine candidates targeting RSV antigens, including pre-F, F, G (A), G (B), M2-1, and N, have shown efficacy against RSV infection in older adults in clinical trial settings. Although vaccine candidates have demonstrated robust neutralising IgG and cellular responses, it is important that research continues to investigate the RSV immune response in order to further understand how the choice of antigenic target site may impact vaccine effectiveness. In this article, we discuss the Phase 3 vaccine candidates being tested in older adults and review the hurdles that must be overcome to achieve effective protection against RSV.