Neurophysiological and Brain Structural Markers of Cognitive Frailty Differ from Alzheimer's Disease.

With increasing life span and prevalence of dementia, it is important to understand the mechanisms of cognitive aging. Here, we focus on a subgroup of the population we term "cognitively frail," defined by reduced cognitive function in the absence of subjective memory complaints, or a clinical diagnosis of dementia. Cognitive frailty is distinct from cognitive impairment caused by physical frailty. It has been proposed to be a precursor to Alzheimer's disease, but may alternatively represent one end of a nonpathologic spectrum of cognitive aging. We test these hypotheses in humans of both sexes, by comparing the structural and neurophysiological properties of a community-based cohort of cognitive frail adults, to people presenting clinically with diagnoses of Alzheimer's disease or mild cognitive impairment, and community-based cognitively typical older adults. Cognitive performance of the cognitively frail was similar to those with mild cognitive impairment. We used a novel cross-modal paired-associates task that presented images followed by sounds, to induce physiological responses of novelty and associative mismatch, recorded by EEG/MEG. Both controls and cognitively frail showed stronger mismatch responses and larger temporal gray matter volume, compared with people with mild cognitive impairment and Alzheimer's disease. Our results suggest that community-based cognitively frail represents a spectrum of normal aging rather than incipient Alzheimer's disease, despite similar cognitive function. Lower lifelong cognitive reserve, hearing impairment, and cardiovascular comorbidities might contribute to the etiology of the cognitive frailty. Critically, community-based cohorts of older adults with low cognitive performance should not be interpreted as representing undiagnosed Alzheimer's disease.SIGNIFICANCE STATEMENT The current study investigates the neural signatures of cognitive frailty in relation to healthy aging and Alzheimer's disease. We focus on the cognitive aspect of frailty and show that, despite performing similarly to the patients with mild cognitive impairment, a cohort of community-based adults with poor cognitive performance do not show structural atrophy or neurophysiological signatures of Alzheimer's disease. Our results call for caution before assuming that cognitive frailty represents latent Alzheimer's disease. Instead, the cognitive underperformance of cognitively frail adults could result in cumulative effects of multiple psychosocial risk factors over the lifespan, and medical comorbidities.

Polypharmacy and medication regimen complexity as factors associated with staff informant rated quality of life in residents of aged care facilities: a cross-sectional study.

PURPOSE: The purpose of this study is to investigate the association between polypharmacy with health-related quality of life (HRQoL) and medication regimen complexity with HRQoL in residential aged care facilities (RACFs). METHODS: A cross-sectional study of 383 residents from six Australian RACFs was conducted. The primary exposures were polypharmacy (≥9 regular medications) and the validated Medication Regimen Complexity Index (MRCI). The outcome measure was staff informant rated quality of life assessed using the Quality of Life Alzheimer's disease (QoL-AD) scale. Covariates included age, sex, Charlson's comorbidity index, activities of daily living, and dementia severity. Logistic quantile regression was used to characterize the association between polypharmacy and QoL-AD (model 1) and MRCI and QoL-AD (model 2). RESULTS: The median age of the 383 residents was 88 years and 297 (78 %) residents were female. In total, 63 % of residents were exposed to polypharmacy and the median MRCI score (range) was 43.5 (4-113). After adjusting for the covariates, polypharmacy was not associated with either higher or lower QoL-AD scores (estimate -0.02; 95 % confidence interval (CI) -0.165, 0.124; p = 0.78). Similarly, after adjusting for the covariates, MRCI was not associated with either higher or lower QoL-AD scores (estimate -0.0009, 95 % CI -0.005, 0.003; p = 0.63). CONCLUSIONS: These findings suggest that polypharmacy and medication regimen complexity are not associated with staff informant rated HRQoL. Further research is needed to investigate how specific medication classes may impact change in quality of life over time.

The association between benzodiazepine use and sleep quality in residential aged care facilities: a cross-sectional study.

BACKGROUND: Benzodiazepines are commonly prescribed in residential aged care facilities (RACFs) for their sedative and anxiolytic effects. The objective of this study was to investigate the association between benzodiazepine use and sleep quality in residents of RACFs. METHODS: A cross-sectional study involving 383 participants was conducted in six Australian RACFs. Night-time sleep quality, day-time drowsiness and day-time napping behavior were assessed using a validated questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the association between benzodiazepine use and sleep quality. Covariates included pain, dementia severity, depression, insomnia and other sedative use. RESULTS: Of the 383 residents (mean age 87.5 years, 77.5% female), 96(25.1%) used a benzodiazepine on a regular basis. Residents who used long-acting benzodiazepines on a regular basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 - 15.15). Residents who used short-acting benzodiazepines on a PRN only basis had longer daytime napping times than non-users (AOR = 1.77, 95%CI 1.01 - 3.08). No benzodiazepine category was associated with day-time drowsiness. CONCLUSIONS: The association between benzodiazepine use and sleep quality is dependent on the half-life and prescribing pattern of the benzodiazepine. Short-acting PRN benzodiazepines were associated with lower night time sleep quality and longer day-time napping compared to long-acting regular benzodiazepines. Longitudinal studies are needed to determine whether these findings reflect channeling of short-acting agents to residents at higher risk of sleep disorders.

Orbito-frontal cortex is necessary for temporal context memory.

Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two complimentary studies: functional magnetic resonance imaging to measure OFC activity associated with successful temporal and spatial context memory during encoding and retrieval in healthy young participants, and a neuropsychological investigation to measure changes in spatial and temporal context memory in OFC lesion patients. Imaging results revealed that OFC contributed to encoding and retrieval of associations between objects and their temporal but not their spatial contexts. Consistent with this, OFC patients exhibited impairments in temporal but not spatial source memory accuracy. These results suggest that OFC plays a critical role in the formation and subsequent retrieval of temporal context.

Cognitive Diversity in a Healthy Aging Cohort: Cross-Domain Cognition in the Cam-CAN Project.

Objective: Studies of "healthy" cognitive aging often focus on a limited set of measures that decline with age. The current study argues that defining and supporting healthy cognition requires understanding diverse cognitive performance across the lifespan. Method: Data from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) cohort was examined across a range of cognitive domains. Performance was related to lifestyle including education, social engagement, and enrichment activities. Results: Results indicate variable relationships between cognition and age (positive, negative, or no relationship). Principal components analysis indicated maintained cognitive diversity across the adult lifespan, and that cognition-lifestyle relationships differed by age and domain. Discussion: Our findings support a view of normal cognitive aging as a lifelong developmental process with diverse relationships between cognition, lifestyle, and age. This reinforces the need for large-scale studies of cognitive aging to include a wider range of both ages and cognitive tasks.

Differentiating the roles of the hippocampus and perirhinal cortex in processes beyond long-term declarative memory: a double dissociation in dementia.

There is increasing evidence to suggest that the hippocampus and perirhinal cortex may mediate processes beyond long-term declarative memory. We assessed patients with Alzheimer's disease (AD) or semantic dementia (SD) on a visual oddity judgment task that did not place an explicit demand on long-term memory and is known to be sensitive to hippocampal and perirhinal cortex lesions. Importantly, within the medial temporal lobe, AD is associated with predominant hippocampal atrophy, whereas SD patients have greater perirhinal cortex damage. The AD group was selectively impaired in oddity judgment for scenes, whereas the SD patients demonstrated a deficit in face oddity judgment only. This compelling double dissociation supports the idea that the hippocampus and perirhinal cortex may be critical for the processing of scenes and objects, respectively, in the domain of perception or very short-term working memory.

Are residents of aged care facilities willing to have their medications deprescribed?

PURPOSE: There has been recent interest in deprescribing, particularly among older people. No previous studies have assessed whether residents of aged care facilities are willing to have their medications deprescribed. Understanding residents' attitudes toward deprescribing is important for developing deprescribing interventions. OBJECTIVE: To investigate residents' willingness to have their medications deprescribed. METHODS: This was a cross-sectional survey of 232 residents aged ≥65 years from six residential aged care facilities (RACFs) across metropolitan and regional South Australia. Overall, 163 of the 232 residents (70.3%) took ≥9 regular medications. All participants completed the 10-item Patients' Attitudes Towards Deprescribing (PATD) questionnaire. RESULTS: Overall, 40.5% of residents reported a desire to stop taking one or more of their medications. If their doctor said it was possible, 78.9% of residents were willing to have one or more of their medications deprescribed. Residents taking ≥9 medications were more likely to feel that they were taking a large number of medications compared to residents taking <9 medications (50.3% vs 14.5%, P < 0.01), and were more likely to believe one or more of their medications was causing side effects (14.7% vs 10.1%, P = 0.02). However, residents taking ≥9 regular medications were not significantly more likely to want to reduce their number of medications than residents taking <9 medications. CONCLUSIONS: Deprescribing interventions are likely to be acceptable to residents' of RACFs, with a high willingness to discontinue medicines if doctors say it is possible. This highlights the importance of the proactive involvement of health care professionals in an individualized deprescribing process.

Analgesic use and pain in residents with and without dementia in aged care facilities: A cross-sectional study.

AIM: To investigate analgesic use and pain in people with and without dementia in Australian residential aged are facilities. METHODS: A cross-sectional study of 383 residents of six residential aged are facilities was conducted. Nurses assessed self-reported and clinician-observed pain. Analgesic use data were extracted from medication charts. Logistic regression was used to investigate factors associated with analgesic use. RESULTS: Analgesics were administered to 291 (76.0%) residents in the previous 24 hours. The prevalence of analgesic use was similar among residents with and without dementia (79.3% vs 73.4%, P = 0.20). Residents with dementia had a higher prevalence of self-reported pain than those without dementia but similar prevalence of clinician-observed pain. In residents with dementia, high care residence and dementia severity were associated with analgesic use. CONCLUSION: The prevalence of analgesic use was similar among residents with and without dementia. Both self-reported and clinician-observed measures are needed in regular pain assessments.

Factors associated with antidepressant use in residents with and without dementia in Australian aged care facilities.

OBJECTIVE: Depressive symptoms are highly prevalent in residential aged care facilities (RACFs). The prevalence of antidepressant use is increasing but the effectiveness of antidepressants in people with dementia is uncertain. The objective of the study was to investigate factors associated with antidepressant use in residents with and without dementia. METHODS: This was a prospective cross-sectional study of 383 residents in six Australian RACFs. Data on health status, medications and demographics were collected by trained study nurses from April to August 2014. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with antidepressant use. Analyses were stratified by dementia and depression. RESULTS: Overall, 183 (47.8%) residents used antidepressants. The prevalence of antidepressant use was similar among residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use in the main analysis (AOR = 0.56, 95% CI = 0.32-0.99) and in subanalyses for residents with documented depression (AOR = 0.51, 95% CI = 0.27-0.96). In residents with dementia, moderate quality of life was associated with a lower odds of antidepressant use compared with poor quality of life (AOR = 0.35, 95% C I= 0.13-0.95). In residents without dementia, analgesic use was associated with antidepressant use (AOR = 2.34, 95% CI = 1.07-5.18). CONCLUSIONS: The prevalence of antidepressant use was similar in residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use but there was no association between self-reported pain and antidepressant use.

Multiple determinants of lifespan memory differences.

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss.

Frailty Levels in Residential Aged Care Facilities Measured Using the Frailty Index and FRAIL-NH Scale.

OBJECTIVES: To compare the FRAIL-NH scale with the Frailty Index in assessing frailty in residential aged care facilities. DESIGN: Cross-sectional. SETTING: Six Australian residential aged care facilities. PARTICIPANTS: Individuals aged 65 and older (N = 383, mean aged 87.5 ± 6.2, 77.5% female). MEASUREMENTS: Frailty was assessed using the 66-item Frailty Index and the FRAIL-NH scale. Other measures examined were dementia diagnosis, level of care, resident satisfaction with care, nurse-reported resident quality of life, neuropsychiatric symptoms, and professional caregiver burden. RESULTS: The FRAIL-NH scale was significantly associated with the Frailty Index (correlation coefficient = 0.81, P < .001). Based on the Frailty Index, 60.8% of participants were categorized as frail and 24.4% as most frail. Based on the FRAIL-NH, 37.5% of participants were classified as frail and 35.9% as most frail. Women were assessed as being frailer than men using both tools (P = .006 for FI; P = .03 for FRAIL-NH). Frailty Index levels were higher in participants aged 95 and older (0.39 ± 0.13) than in those aged younger than 85 (0.33 ± 0.13; P = .008) and in participants born outside Australia (0.38 ± 0.13) than in those born in Australia (0.34 ± 0.13; P = .01). Both frailty tools were associated with most characteristics that would indicate higher care needs, with the Frailty Index having stronger associations with all of these measures. CONCLUSION: The FRAIL-NH scale is a simple and practical method to screen for frailty in residential aged care facilities.

Polypharmacy and Medication Regimen Complexity as Risk Factors for Hospitalization Among Residents of Long-Term Care Facilities: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between polypharmacy and medication regimen complexity with time to first hospitalization, number of hospitalizations, and number of hospital days over a 12-month period. DESIGN: A 12-month prospective cohort study. PARTICIPANTS AND SETTING: A total of 383 residents of 6 Australian long-term care facilities (LTCFs). MEASUREMENTS: The primary exposures were polypharmacy (≥9 regular medications) and the 65-item Medication Regimen Complexity Index (MRCI). Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between polypharmacy and MRCI with time to first hospitalization. Poisson regression was used to compute incident rate ratios (IRR) and 95% CIs for the association between polypharmacy and MRCI with number of hospitalizations and number of hospital days. Models were adjusted for age, sex, length of stay in LTCF, comorbidities, activities of daily living, and dementia severity. RESULTS: There were 0.56 (95% CI 0.49-0.65) hospitalizations per person-year and 4.52 (95% CI 4.31-4.76) hospital days per person-year. In adjusted analyses, polypharmacy was associated with time to first hospitalization (HR 1.84; 95% CI 1.21-2.79), number of hospitalizations (IRR 1.51; 95% CI 1.09-2.10), and hospital days per person-year (IRR 1.39; 95% CI 1.24-1.56). Similarly, in adjusted analyses a 10-unit increase in MRCI was associated with time to first hospitalization (HR 1.17; 95% CI 1.06-1.29), number of hospitalizations (IRR 1.15; 95% CI 1.06-1.24), and hospital days per person-year (IRR 1.19; 95% CI 1.16-1.23). CONCLUSIONS: Polypharmacy and medication regimen complexity are associated with hospitalizations from LTCFs. This highlights the importance of regular medication review for residents of LTCFs and the need for further research into the risk-to-benefit ratio of prescribing in this setting.

Analgesic Use and Daytime Sleepiness in Residents With and Without Dementia in Residential Aged Care Facilities.

BACKGROUND: Managing pain in residents of residential aged care facilities (RACFs) is challenging, especially for people with dementia. Clinicians must weigh the benefits of analgesic use against the potential for adverse events, particularly daytime sleepiness. OBJECTIVES: The aim was to investigate the association between analgesic use and daytime sleepiness in residents with and without dementia in RACFs. METHODS: This was a cross-sectional study of 383 permanent residents from six low-level and high-level RACFs in South Australia. Main measures included analgesic use in the previous 24 h, analgesic load and self-reported daytime sleepiness. Covariates included relevant comorbidities (insomnia, depression, painful conditions), Charlson's Comorbidity Index, sedative load, self-reported and clinician-observed pain and dementia severity. Logistic regression was used to compute odds ratios (ORs) and confidence intervals (CIs) for the association between analgesic use and daytime sleepiness. RESULTS: Analgesics were used by 288 residents (75.2%) in the previous 24 h. These included paracetamol (n = 264, 68.9%), opioids (n = 110, 28.7%) and oral NSAIDs (n = 14, 3.7%). Overall, 116 (30.3%) residents were categorized as having daytime sleepiness. Of those with dementia, 77 (45.6%) were categorized as having daytime sleepiness. Opioid use in the previous 24 h was not associated with daytime sleepiness in unadjusted or adjusted analyses. Paracetamol use was positively associated with daytime sleepiness (OR 2.31; 95% CI 1.20-4.42). CONCLUSION: Although daytime sleepiness occurred in a large number of residents, especially those with dementia, this sleepiness was not necessarily associated with use of opioids. The risk of opioid-induced sedation may have been managed by strategies including preferential prescribing of paracetamol to residents at risk of sleepiness, opioid discontinuation in residents who experienced sleepiness, and use of low doses of opioids.

Analgesic use, pain and daytime sedation in people with and without dementia in aged care facilities: a cross-sectional, multisite, epidemiological study protocol.

INTRODUCTION: People living with dementia may experience and express pain in different ways to people without dementia. People with dementia are typically prescribed fewer analgesics than people without dementia indicating a potential difference in how pain is identified and treated in these populations. The objectives of this study are to (1) investigate the prevalence of analgesic load, pain and daytime sedation in people with and without dementia in Australian residential aged care facilities (RACFs), and (2) investigate the clinical and diagnostic associations between analgesic load, pain and daytime sedation in people with and without dementia in Australian RACFs. METHODS/ANALYSIS: This will be a cross-sectional study of 300 permanent residents of up to 10 low-level and high-level RACFs in South Australia with and without dementia. Trained study nurses will administer validated and dementia-specific assessments of self-reported and clinician-observed pain, sedation and other clinical and humanistic outcomes. Medicine-use data will be extracted directly from each resident's medication administration chart. Binary and multinominal logistic regression will be used to compute unadjusted and adjusted ORs and 95% CIs for factors associated with pain, analgesic load and daytime sedation. These factors will include dementia severity, behavioural and psychological symptoms, quality of life, resident satisfaction, attitudes towards medicines, activities of daily living and nutritional status. ETHICS AND DISSEMINATION: Institutional ethics approval has been granted. The findings will be disseminated through public lectures, professional and scientific conferences and in peer-reviewed journal articles. The findings of this study will allow for a better understanding of the prevalence and factors associated with analgesic use, pain and other outcomes in residential care. The findings of this study will be used to inform the development and implementation of strategies to improve the quality of life of people with dementia.