Dissonance in the face of Alzheimer's disease breakthroughs: clinician and lay stakeholder acceptance, concerns and willingness to pay for emerging disease-modifying therapies.

BACKGROUND: Introducing new disease-modifying therapies (DMTs) for Alzheimer's disease demands a fundamental shift in diagnosis and care for most health systems around the world. Understanding the views of health professionals, potential patients, care partners and taxpayers is crucial for service planning and expectation management about these new therapies. AIMS: To investigate the public's and professionals' perspectives regarding (1) acceptability of new DMTs for Alzheimer's disease; (2) perceptions of risk/benefits; (3) the public's willingness to pay (WTP). METHOD: Informed by the 'theoretical framework of acceptability', we conducted two online surveys with 1000 members of the general public and 77 health professionals in Ireland. Descriptive and multivariate regression analyses examined factors associated with DMT acceptance and WTP. RESULTS: Healthcare professionals had a higher acceptance (65%) than the general public (48%). Professionals were more concerned about potential brain bleeds (70%) and efficacy (68%), while the public focused on accessibility and costs. Younger participants (18-24 years) displayed a higher WTP. Education and insurance affected WTP decisions. CONCLUSIONS: This study exposes complex attitudes toward emerging DMTs for Alzheimer's disease, challenging conventional wisdom in multiple dimensions. A surprising 25% of the public expressed aversion to these new treatments, despite society's deep-rooted fear of dementia in older age. Healthcare professionals displayed nuanced concerns, prioritising clinical effectiveness and potential brain complications. Intriguingly, younger, better-educated and privately insured individuals exhibited a greater WTP, foregrounding critical questions about healthcare equity. These multifaceted findings serve as a guidepost for healthcare strategists, policymakers and ethicists as we edge closer to integrating DMTs into Alzheimer's disease care.

New horizons in the diagnosis and management of Alzheimer's Disease in older adults.

Alzheimer's Disease (ad) is the most common cause of dementia, and in addition to cognitive decline, it directly contributes to physical frailty, falls, incontinence, institutionalisation and polypharmacy in older adults. Increasing availability of clinically validated biomarkers including cerebrospinal fluid and positron emission tomography to assess both amyloid and tau pathology has led to a reconceptualisation of ad as a clinical-biological diagnosis, rather than one based purely on clinical phenotype. However, co-pathology is frequent in older adults which influence the accuracy of biomarker interpretation. Importantly, some older adults with positive amyloid or tau pathological biomarkers may never experience cognitive impairment or dementia. These strides towards achieving an accurate clinical-biological diagnosis are occurring alongside recent positive phase 3 trial results reporting statistically significant effects of anti-amyloid Disease-Modifying Therapies (DMTs) on disease severity in early ad. However, the real-world clinical benefit of these DMTs is not clear and concerns remain regarding how trial results will translate to real-world clinical populations, potential adverse effects (including amyloid-related imaging abnormalities), which can be severe and healthcare systems readiness to afford and deliver potential DMTs to appropriate populations. Here, we review recent advances in both clinical-biological diagnostic classification and future treatment in older adults living with ad. Advocating for access to both more accurate clinical-biological diagnosis and potential DMTs must be done so in a holistic and gerontologically attuned fashion, with geriatricians advocating for enhanced multi-component and multi-disciplinary care for all older adults with ad. This includes those across the ad severity spectrum including older adults potentially ineligible for emerging DMTs.

Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study.

INTRODUCTION: Problematic polypharmacy is the prescribing of five or more medications potentially inappropriately. Unintentional prescribing cascades represent an under-researched aspect of problematic polypharmacy and occur when an adverse drug reaction (ADR) is misinterpreted as a new symptom resulting in the initiation of a new medication. The aim of this study was to elicit key stakeholders' perceptions of and attitudes towards problematic polypharmacy, with a focus on prescribing cascades. METHODS: qualitative one-to-one semi-structured interviews were conducted with predefined key stakeholder groups. Inductive thematic analysis was employed. RESULTS: Thirty-one stakeholders were interviewed: six patients, two carers, seven general practitioners, eight pharmacists, four hospital doctors, two professional organisation representatives and two policymakers. Three main themes were identified: (i) ADRs and prescribing cascades-a necessary evil. Healthcare professionals (HCPs) expressed concern that experiencing an ADR would negatively impact patients' confidence in their doctor. However, patients viewed ADRs pragmatically as an unpredictable risk. (ii) Balancing the risk/benefit tipping point. The complexity of prescribing decisions in the context of polypharmacy made balancing this tipping point challenging. Consequently, HCPs avoided medication changes. (iii) The minefield of medication reconciliation. Stakeholders, including patients and carers, viewed medication reconciliation as a perilous activity due to systemic communication deficits. CONCLUSION: Stakeholders believed that at a certain depth of polypharmacy, the risk that a new symptom is being caused by an existing medication becomes incalculable. Therefore, in the absence of harm, medication changes were avoided. However, medication reconciliation post hospital discharge compelled prescribing decisions and was seen as a high-risk activity by stakeholders.

Discrete Relationships between Spatiotemporal Gait Characteristics and Domain-Specific Neuropsychological Performance in Midlife.

Midlife risk factors such as type 2 diabetes mellitus (T2DM) confer a significantly increased risk of cognitive impairment in later life with executive function, memory, and attention domains often affected first. Spatiotemporal gait characteristics are emerging as important integrative biomarkers of neurocognitive function and of later dementia risk. We examined 24 spatiotemporal gait parameters across five domains of gait previously linked to cognitive function on usual-pace, maximal-pace, and cognitive dual-task gait conditions in 102 middle-aged adults with (57.5 ± 8.0 years; 40% female) and without (57.0 ± 8.3 years; 62.1% female) T2DM. Neurocognitive function was measured using a neuropsychological assessment battery. T2DM was associated with significant changes in gait phases and rhythm domains at usual pace, and greater gait variability observed during maximal pace and dual tasks. In the overall cohort, both the gait pace and rhythm domains were associated with memory and executive function during usual pace. At maximal pace, gait pace parameters were associated with reaction time and delayed memory. During the cognitive dual task, associations between gait variability and both delayed memory/executive function were observed. Associations persisted following covariate adjustment and did not differ by T2DM status. Principal components analysis identified a consistent association of slower gait pace (step/stride length) and increased gait variability during maximal-pace walking with poorer memory and executive function performance. These data support the use of spatiotemporal gait as an integrative biomarker of neurocognitive function in otherwise healthy middle-aged individuals and reveal discrete associations between both differing gait tasks and gait domains with domain-specific neuropsychological performance. Employing both maximal-pace and dual-task paradigms may be important in cognitively unimpaired populations with risk factors for later cognitive decline-with the aim of identifying individuals who may benefit from potential preventative interventions.

A qualitative study to inform adaptations to a brain health intervention for older adults with type 2 diabetes living in rural regions of Ireland.

AIMS: Type 2 diabetes is a risk factor for late-life dementia, but dementia prevention strategies have yet to be comprehensively evaluated in people with diabetes. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated cognitive benefits of a 2-year multidomain lifestyle intervention. However, given the intensive nature of FINGER, there is uncertainty about whether it can be implemented in other high-risk populations. Our aim was to explore attitudes towards dementia risk, and barriers to an intervention based on the FINGER model in older adults with type 2 diabetes living in rural areas of Ireland. METHODS: Focus groups were conducted with 21 adults (11 men and 10 women) aged 60+ years with type 2 diabetes living in border regions of north and south Ireland. Data were analysed using thematic analysis. RESULTS: There was limited understanding of diabetes as a risk factor for late-life dementia. The main barriers to engagement with the multidomain intervention were eating foods that were not compatible with cultural norms, time and travel constraints, and perceived lack of self-efficacy and self-motivation for adopting the desired diet, exercise and computerised cognitive training (CCT) behaviours. Facilitators for intervention acceptability included the provision of culturally tailored and personalised education, support from a trusted source, and inclusion of goal setting and self-monitoring behavioural strategies. CONCLUSIONS: While there was high acceptability for a brain health intervention, several barriers including cultural food norms and low self-efficacy for adopting the diet, exercise and CCT components would need to be considered in the intervention design. Findings from this study will be used to inform local decisions regarding the adaptation of FINGER for people with type 2 diabetes. The feasibility of the adapted multidomain intervention will then be evaluated in a future pilot trial.

Safety and feasibility of transcutaneous vagus nerve stimulation in mild cognitive impairment: VINCI-AD study protocol.

BACKGROUND: Over 55 million adults are living with dementia globally, which is projected to reach 157 million by 2050. Mild cognitive impairment (MCI), a syndrome of memory impairment with intact activities of daily living, may precede dementia by several years. Around 5-15% of individuals with MCI convert to dementia annually. Novel treatments which delay progression of MCI to dementia are urgently needed. Transcutaneous vagal nerve stimulation (tVNS) is a non-invasive neuromodulation technique that targets the vagus nerve. Importantly, tVNS has been shown to improve cognition in healthy volunteers, but has not been extensively examined as a potential therapeutic approach in MCI. VINCI-AD will examine the safety and feasibility of tVNS in older adults with MCI. DESIGN: VINCI-AD is an investigator-led, single-site, single-blind, sham-controlled crossover pilot study which aims to assess the safety and feasibility of tVNS in 40 participants with amnestic MCI. All participants will attend for three consecutive study visits during which they will be randomised to receive no stimulation (baseline), active tVNS stimulation (stimulation at cymba conchae of left ear) or sham tVNS stimulation (at earlobe). Safety will be primarily assessed by ascertainment of adverse events. Further safety assessment will examine the impact of acute tVNS on subjective (orthostatic symptoms), peripheral (finometry-based blood pressure) and central (assessed via Near Infrared Spectroscopy [NIRS]) haemodynamic responses to active stand. Feasibility will be determined using a custom-designed occupational assessment of device usability. Exploratory secondary analysis in VINCI-AD will examine the potential impact of acute tVNS on associative memory, spatial memory and inhibitory control to inform sample size estimates for future trials of tVNS in older adults with MCI. DISCUSSION: VINCI-AD will report on the safety (adverse events/haemodynamic responses to active stand) and feasibility of tVNS as a potential therapeutic option in MCI. Detailed reporting of study eligibility and completion rates will be reported. Exploratory analysis will examine the potential cognitive benefits of acute tVNS on cognitive function in MCI to report potential effect sizes that may inform future clinical trials in this cohort. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05514756 . Trial Registration Number NCT05514756 (24th August 2022 for this protocol, version 1.0.).

The 'Bermuda Triangle' of orthostatic hypotension, cognitive impairment and reduced mobility: prospective associations with falls and fractures in The Irish Longitudinal Study on Ageing.

BACKGROUND: Orthostatic hypotension (OH), cognitive impairment (Cog) and mobility impairment (MI) frequently co-occur in older adults who fall. This study examines clustering of these three geriatric syndromes and ascertains their relationship with future falls/fractures in a large cohort of community-dwelling people ≥ 65 years during 8-year follow-up. METHODS: OH was defined as an orthostatic drop ≥ 20 mmHg in systolic blood pressure (from seated to standing) and/or reporting orthostatic unsteadiness. CI was defined as Mini Mental State Examination ≤ 24 and/or self-reporting memory as fair/poor. MI was defined as Timed Up and Go ≥12 s. Logistic regression models, including three-way interactions, assessed the longitudinal association with future falls (explained and unexplained) and fractures. RESULTS: Almost 10% (88/2,108) of participants had all three Bermuda syndromes. One-fifth of participants had an unexplained fall during follow-up, whereas 1/10 had a fracture. There was a graded relationship with incident unexplained falls and fracture as the number of Bermuda syndromes accumulated. In fully adjusted models, the cluster of OH, CI and MI was most strongly associated with unexplained falls (odds ratios (OR) 4.33 (2.59-7.24); P < 0.001) and incident fracture (OR 2.51 (1.26-4.98); P = 0.045). Other clusters significantly associated with unexplained falls included OH; CI and MI; MI and OH; CI and OH. No other clusters were associated with fracture. DISCUSSION: The 'Bermuda Triangle' of OH, CI and MI was independently associated with future unexplained falls and fractures amongst community-dwelling older people. This simple risk identification scheme may represent an ideal target for multifaceted falls prevention strategies in community-dwelling older adults.

Potential eligibility for Aducanumab therapy in an Irish specialist cognitive service-Utilising cerebrospinal fluid biomarkers and appropriate use criteria.

OBJECTIVES: Aducanumab is a monoclonal antibody which has recently been licenced for use by the food and drug administration for treatment of patients with mild cognitive impairment due to Alzheimer's disease (AD) or mild AD dementia. Appropriate use criteria (AUC) for Aducanumab in clinical practice are available. We look to review patients in our specialist interdisciplinary cognitive service with positive cerebrospinal fluid (CSF) biomarkers for AD for their hypothetical eligibility for Aducanumab, or a similar anti-amyloid agent. METHODS: Retrospective analysis was undertaken of patients with positive AD-biomarker CSF analysis. Data available at time of CSF analysis was reviewed to determine hypothetical eligibility for Aducanumab. RESULTS: Seventy patients had positive AD-CSF biomarkers. Forty nine of these were seen in the Gerontology-led service, with 21 in the neurology cohort. Average patient age was 70 years old. Forty patients (57%) met eligibility criteria for Aducanumab therapy by AUC guidelines. CONCLUSION: We highlight the patients within our service who would be appropriate for Aducanumab or similar anti-amyloid agents should licencing be granted in the European Union, and the need to develop the resources and capacity to deliver this or other emerging disease modifying AD therapies. CLINICAL TRIAL REGISTRATION: All patients in the combined cognitive clinic provide consent re willingness to be contacted re research.

Gait Characteristics and Cognitive Function in Middle-Aged Adults with and without Type 2 Diabetes Mellitus: Data from ENBIND.

Type 2 Diabetes Mellitus (T2DM) in midlife is associated with a greater risk of dementia in later life. Both gait speed and spatiotemporal gait characteristics have been associated with later cognitive decline in community-dwelling older adults. Thus, the assessment of gait characteristics in uncomplicated midlife T2DM may be important in selecting-out those with T2DM at greatest risk of later cognitive decline. We assessed the relationship between Inertial Motion Unit (IMUs)-derived gait characteristics and cognitive function assessed via Montreal Cognitive Assessment (MoCA)/detailed neuropsychological assessment battery (CANTAB) in middle-aged adults with and without uncomplicated T2DM using both multivariate linear regression and a neural network approach. Gait was assessed under (i) normal walking, (ii) fast (maximal) walking and (iii) cognitive dual-task walking (reciting alternate letters of the alphabet) conditions. Overall, 138 individuals were recruited (n = 94 with T2DM; 53% female, 52.8 ± 8.3 years; n = 44 healthy controls, 43% female, 51.9 ± 8.1 years). Midlife T2DM was associated with significantly slower gait velocity on both slow and fast walks (both p < 0.01) in addition to a longer stride time and greater gait complexity during normal walk (both p < 0.05). Findings persisted following covariate adjustment. In analyzing cognitive performance, the strongest association was observed between gait velocity and global cognitive function (MoCA). Significant associations were also observed between immediate/delayed memory performance and gait velocity. Analysis using a neural network approach did not outperform multivariate linear regression in predicting cognitive function (MoCA) from gait velocity. Our study demonstrates the impact of uncomplicated T2DM on gait speed and gait characteristics in midlife, in addition to the striking relationship between gait characteristics and global cognitive function/memory performance in midlife. Further studies are needed to evaluate the longitudinal relationship between midlife gait characteristics and later cognitive decline, which may aid in selecting-out those with T2DM at greatest-risk for preventative interventions.

Long-term antipsychotic use and cognitive decline in community-dwelling older adults with mild-moderate Alzheimer disease: Data from NILVAD.

INTRODUCTION: Previous evidence has suggested that antipsychotic use may be associated with accelerated cognitive decline in those living with dementia. However, the cognitive effects of long-term antipsychotic use in community-dwelling older adults with mild-moderate Alzheimer disease (AD) has not been explored to date. METHODS: We assessed the impact of long-term antipsychotic use on the rate of cognitive decline (Alzheimer's Disease Assessment Scale-Cognitive Subsection) and dementia progression (Clinical Dementia Rating-Sum of Boxes [CDR-Sb]/Disability Assessment for Dementia [DAD]) over 18 months in older adults with mild-moderate AD. RESULTS: Of 509 participants with mild-moderate AD, one-tenth (54/509; 10.6%) were prescribed an antipsychotic for the 18-month study duration. Antipsychotic use was significantly associated with accelerated cognitive decline at both 12 (ß: 3.53, 0.91-6.17, p = 0.008) and 18 months (ß: 3.81, 0.49-7.14, p = 0.024) in addition to greater dementia progression at both 12 (ß: 1.85, -0.97-2.73, p < 0.001 for CDR-Sb/ß: -3.33, -5.56-1.10, p = 0.003 for DAD) and 18 months (ß: 1.41, 0.16-2.67, p = 0.027 for CDR-Sb/ß: -3.86, -6.64 to -1.08, p = 0.006 for DAD). APOE ε4 carriers experienced significantly greater cognitive decline with long-term antipsychotic use. CONCLUSIONS: Long-term antipsychotic use was associated with greater cognitive decline and dementia progression in community-dwelling older adults with mild-moderate AD. Our findings are consistent with previous evidence encouraging cautious and careful consideration of risks versus benefits of antipsychotic usage in those with AD.

Asymptomatic carriage rates and case fatality of SARS-CoV-2 infection in residents and staff in Irish nursing homes.

BACKGROUND: SARS-CoV-2 has disproportionately affected nursing homes (NH). In Ireland, the first NH case COVID-19 occurred on 16 March 2020. A national point-prevalence testing programme of all NH residents and staff took place (18 April 2020 to 5 May 2020). AIMS: to examine characteristics of NHs across three Irish Community Health Organisations, proportions with COVID-19 outbreaks, staff and resident infection rates symptom profile and resident case fatality. METHODS: in total, 45 NHs surveyed, requesting details on occupancy, size, COVID-19 outbreak, outbreak timing, total symptomatic/asymptomatic cases and outcomes for residents from 29 February 2020 to 22 May 2020. RESULTS: surveys were returned from 62.2% (28/45) of NHs (2,043 residents, 2,303 beds). Three-quarters (21/28) had COVID-19 outbreaks (1,741 residents, 1,972 beds). Median time from first COVID-19 case in Ireland to first case in these NHs was 27.0 days. Resident incidence was 43.9% (764/1,741)-40.8% (710/1,741) laboratory confirmed, with 27.2% (193/710) asymptomatic and 3.1% (54/1,741) clinically suspected. Resident case fatality was 27.6% (211/764) for combined laboratory-confirmed/clinically suspected COVID-19. Similar proportions of residents in NHs with 'early-stage' (<28 days) versus 'later-stage' outbreaks developed COVID-19. Lower proportions of residents in 'early' outbreak NHs had recovered compared with those with 'late' outbreaks (37.4 versus 61.7%; χ2 = 56.9, P < 0.001). Of 395 NH staff across 12 sites with confirmed COVID-19, 24.7% (99/398) were asymptomatic. There was a significant correlation between the proportion of staff with symptomatic COVID-19 and resident numbers with confirmed/suspected COVID-19 (Spearman's rho = 0.81, P < 0.001). CONCLUSION: this study demonstrates the significant impact of COVID-19 on the NH sector. Systematic point-prevalence testing is necessary to reduce risk of transmission from asymptomatic carriers and manage outbreaks in this setting.

Embedding audiological screening within memory clinic care pathway for individuals at risk of cognitive decline-patient perspectives.

BACKGROUND: With the evolving knowledge on hearing as a potentially modifiable mid-life risk factor for dementia, identification of people at risk becomes increasingly important. People with mild cognitive impairment (MCI) presenting to specialist memory services represent a key "at-risk" target population for audiological evaluation, but few services have established this pathway. This study sought to examine the patient experience and understanding of this process. METHODS: All patients with MCI attending a tertiary referral memory service referred for audiology review were contacted. A patient survey was delivered over the phone. Outpatient letters and the memory clinic database were reviewed. RESULTS: Twenty patients with MCI were included in the survey. Eight (8/20, 40%) had self-reported hearing loss. Upon formal audiological assessment seventeen (17/20, 85%) had objective evidence of hearing loss; nine (9/17, 52.9%) with mild-moderate and eight (8/17, 47%) with moderate-severe hearing loss. Only six patients (6/20, 30%) recalled having the rationale behind having a hearing test as part of their memory work-up explained to them. However, the majority (15/20, 75%) felt a hearing test was an important part of their memory assessment. Just seven patients overall (7/20, 35%) identified a link between hearing-loss and cognition. All patients who provided feedback on the service itself made positive comments, although (4/20, 20%) felt they did not get adequate information about the results. CONCLUSIONS: A significant proportion of people with MCI had de-novo evidence of hearing impairment upon assessment. Patients are satisfied with incorporating audiological evaluation into a memory clinic assessment, however clear communication around indication, recommendations, and follow-up ensuring compliance is required.

Personal Electronic Records of Medications (PERMs) for medication reconciliation at care transitions: a rapid realist review.

BACKGROUND: Medication reconciliation (MedRec), a process to reduce medication error at care transitions, is labour- and resource-intensive and time-consuming. Use of Personal Electronic Records of Medications (PERMs) in health information systems to support MedRec have proven challenging. Relatively little is known about the design, use or implementation of PERMs at care transitions that impacts on MedRec in the 'real world'. To respond to this gap in knowledge we undertook a rapid realist review (RRR). The aim was to develop theories to explain how, why, when, where and for whom PERMs are designed, implemented or used in practice at care transitions that impacts on MedRec. METHODOLOGY: We used realist methodology and undertook the RRR between August 2020 and February 2021. We collaborated with experts in the field to identify key themes. Articles were sourced from four databases (Pubmed, Embase, CINAHL Complete and OpenGrey) to contribute to the theory development. Quality assessment, screening and data extraction using NVivo was completed. Contexts, mechanisms and outcomes configurations were identified and synthesised. The experts considered these theories for relevance and practicality and suggested refinements. RESULTS: Ten provisional theories were identified from 19 articles. Some theories relate to the design (T2 Inclusive design, T3 PERMs complement existing good processes, T7 Interoperability), some relate to the implementation (T5 Tailored training, T9 Positive impact of legislation or governance), some relate to use (T6 Support and on-demand training) and others relate iteratively to all stages of the process (T1 Engage stakeholders, T4 Build trust, T8 Resource investment, T10 Patients as users of PERMs). CONCLUSIONS: This RRR has allowed additional valuable data to be extracted from existing primary research, with minimal resources, that may impact positively on future developments in this area. The theories are interdependent to a greater or lesser extent; several or all of the theories may need to be in play to collectively impact on the design, implementation or use of PERMs for MedRec at care transitions. These theories should now be incorporated into an intervention and evaluated to further test their validity.

Social networks in mild-to-moderate Alzheimer disease: longitudinal relationships with dementia severity, cognitive function, and adverse events.

OBJECTIVES: Poor social networks are associated with a greater likelihood of cognitive decline, dementia, and other adverse health outcomes in later life. However, these relationships have been poorly explored in those with established Alzheimer Disease (AD), who may represent a particularly vulnerable group. METHODS: Analysis of data from the NILVAD study. We assessed social networks (Lubben Social Network Scale [LSNS]), cognition (Alzheimer's disease Assessment Scale [ADAS-Cog]) and dementia severity (Clinical Dementia Rating, Sum of Boxes [CDR-Sb]) in older adults with mild-moderate AD at baseline and at 18 months. RESULTS: 464 participants with mild-to-moderate AD were included (73.1 ± 8.3 years; 61.9% female). At baseline, a poor social network was significantly associated with a greater dementia severity, but not greater cognitive impairment. Rather than a poor social network predicting greater cognitive decline over 18 months, a greater baseline dementia severity predicted a decline in social network over 18 months (ß: -0.22, -0.42 - -0.02, p = 0.034). Finally, a poor social network was associated with a significantly increased likelihood of experiencing serious adverse events (IRR: 1.41, 1.06-1.89, p = 0.019). DISCUSSION: As dementia progresses, older adults with AD are more likely to experience a decline in social network. Further, having a poor social network was associated with a greater likelihood of experiencing serious adverse events. These findings add novel insight into the complex relationship between social networks, dementia progression and adverse events in AD, and underscore the importance of developing and maintaining social networks in AD.

Antidepressant use and orthostatic hypotension in older adults living with mild-to-moderate Alzheimer disease.

OBJECTIVES: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. METHODS: We performed a cross-sectional analysis of baseline data from the NILVAD study. Participants with mild-moderate AD were recruited from 23 centres in nine countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 and 5 minutes of standing. OH was defined as a drop of ≥20 mmHg SBP/≥10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. RESULTS: Of 509 participants (72.9 ± 8.3 years, 61.9% female), two-fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (ß: 1.83, 0.16-3.50, P = .03 for SBP; ß: 1.13, 0.02-2.25, P < .05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1-3.6, P = .02). Both findings persisted following robust covariate adjustment. CONCLUSIONS: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort.

Potentially inappropriate medication use in older adults with mild-moderate Alzheimer's disease: prevalence and associations with adverse events.

AIM: Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer's Disease (AD), who may represent a particularly vulnerable group. DESIGN: Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. SETTING AND PARTICIPANTS: 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. RESULTS: Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13-1.19, P < 0.001), serious adverse events (IRR 1.27; 1.17-1.37, P < 0.001), unscheduled hospitalisations (IRR 1.16, 1.03-1.30, P = 0.016) and GP visits (IRR 1.22, 1.15-1.28, P < 0.001). PIM use was not associated with dementia progression. CONCLUSIONS AND IMPLICATIONS: PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted.

Gait speed, cognition and falls in people living with mild-to-moderate Alzheimer disease: data from NILVAD.

BACKGROUND: Previous evidence suggests that slower gait speed is longitudinally associated with cognitive impairment, dementia and falls in older adults. Despite this, the longitudinal relationship between gait speed, cognition and falls in those with a diagnosis of dementia remains poorly explored. We sought to assess this longitudinal relationship in a cohort of older adults with mild to-moderate Alzheimer Disease (AD). METHODS: Analysis of data from NILVAD, an 18-month randomised-controlled trial of Nilvadipine in mild to moderate AD. We examined: (i) the cross-sectional (baseline) association between slow gait speed and cognitive function, (ii) the relationship between baseline slow gait speed and cognitive function at 18 months (Alzheimer Disease Assessment Scale, Cognitive Subsection: ADAS-Cog), (iii) the relationship between baseline cognitive function and incident slow gait speed at 18 months and finally (iv) the relationship of baseline slow gait speed and incident falls over the study period. RESULTS: Overall, one-tenth (10.03%, N = 37/369) of participants with mild-to-moderate AD met criteria for slow gait speed at baseline and a further 14.09% (N = 52/369) developed incident slow gait speed at 18 months. At baseline, there was a significant association between poorer cognition and slow gait speed (OR 1.05, 95% CI 1.01-1.09, p = 0.025). Whilst there was no association between baseline slow gait speed and change in ADAS-Cog score at 18 months, a greater cognitive severity at baseline predicted incident slow gait speed over 18 months (OR 1.04, 1.01-1.08, p = 0.011). Further, slow gait speed at baseline was associated with a significant risk of incident falls over the study period, which persisted after covariate adjustment (IRR 3.48, 2.05-5.92, p < 0.001). CONCLUSIONS: Poorer baseline cognition was associated with both baseline and incident slow gait speed. Slow gait speed was associated with a significantly increased risk of falls over the study period. Our study adds further evidence to the complex relationship between gait and cognition in this vulnerable group and highlights increased falls risk in older adults with AD and slow gait speed. TRIAL REGISTRATION: Secondary analysis of the NILVAD trial (Clincaltrials.gov NCT02017340; EudraCT number 2012-002764-27). First registered: 20/12/2013.

The association between frontal lobe perfusion and depressive symptoms in later life.

BACKGROUND: Deficits in frontal lobe perfusion have been demonstrated in late-life depression; however, studies to date have generally involved small numbers, used neuroimaging rather than bedside testing and have not controlled for important covariates.AimsWe aimed to examine the association between depressive symptoms and frontal lobe perfusion during standing, in a large cohort of community-dwelling older people. METHOD: Participants aged ≥50 years underwent continuous measurement of orthostatic blood pressure by finometry, and frontal lobe perfusion by near-infrared spectroscopy. Depressive symptoms were assessed by the eight-item Centre for Epidemiological Studies Depression Scale. Real-time frontal lobe cerebral oxygenation was measured by the Portalite System, detecting changes in frontal lobe perfusion and reporting a tissue saturation index score. RESULTS: Almost 8% (209 out of 2616) had clinically significant depressive symptoms. Multilevel models demonstrated a significantly lower tissue saturation index in participants with depressive symptoms at both 60 and 90 s post-stand, with coefficients of -0.43 (95% CI -0.63 to -0.22) and -0.37 (95% CI -0.57 to -0.16), respectively. Controlling for relevant covariates did not significantly attenuate these associations. After addition of systolic blood pressure this association was no longer significant, suggesting lower blood pressure may modify this relationship. CONCLUSIONS: This study demonstrates that lower frontal lobe perfusion, related to lower values of baseline systolic blood pressure, is associated with clinically significant depressive symptoms in a cohort of community-dwelling older people. Given the recognised longitudinal association between lower blood pressure and depression in older people, this may represent a potential therapeutic target for prevention of incident depression.Declaration of interestNone.

What is the Longitudinal Relationship between Gait Abnormalities and Depression in a Cohort of Community-Dwelling Older People? Data From the Irish Longitudinal Study on Ageing (TILDA).

OBJECTIVE: Does baseline gait disturbance predict incident depression in a cohort of community-dwelling older people? METHODS: This is a longitudinal study, embedded within the Irish Longitudinal Study on Ageing (TILDA), examining the association between baseline depression and incident gait abnormalities, as well as between baseline gait abnormalities and incident depression at 2 year follow-up. Depression was defined as a score of ≥16 on the Centre for Epidemiological Studies Depression Scale (CES-D). Gait abnormality was defined as a Timed Up and Go Test (TUG) ≥12 seconds. Assessments were carried out at baseline and at 2 year follow-up. RESULTS: 7% (179/2,638) had baseline depression and 11% (296/2,638) had a gait abnormality at baseline. The incidence of new-onset depression and gait abnormality at Wave 2 was 4% (95/2,364) and 13% (308/2,342) respectively. Logistic regression models demonstrated that baseline gait abnormality was a significant predictor of incident depression with an Incidence Rate Ratio (IRR) of 2.00 (95% CI: 1.18 - 3.40, p =0.010, t =2.57, df =625), which was not attenuated after controlling for covariates. Baseline depression was a predictor of incident gait abnormality at Wave 2 with an IRR of 1.68 (95% CI: 1.16 - 2.43, p =0.006, t =2.75, df =625) but this association was no longer statistically significant when analysis was adjusted for clinical variables. CONCLUSIONS: This study demonstrates that baseline gait disturbance, measured by TUG, predicts incident depression, defined by CES-D, in a population-representative cohort of community-dwelling older people. Possible biological mechanisms for this relationship include white matter disease and executive dysfunction.

Does baseline depression increase the risk of unexplained and accidental falls in a cohort of community-dwelling older people? Data from The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Depression independently increases the risk of falls in older people, but the mechanism for this relationship, as well as the specific falls type involved, remains unclear. Accidental falls (AFs) are due to slips or trips, while the cause of unexplained falls (UFs) is not immediately apparent and can include unrecognised syncope. METHOD: This longitudinal study examines the relationship between baseline depression and subsequent falls, both accidental and unexplained, at 2-year follow-up in a cohort of community dwelling adults aged ≥50 years. Baseline depression was defined as a score ≥16 on The Centre for Epidemiological Studies Depression Scale. At follow-up, participants were assessed regarding falls since last interview. RESULTS: One-third (228/647) of the depressed group had fallen at follow-up, compared with 22% (1388/6243) of the nondepressed group (P < .001). Multiple logistic regression models demonstrated that depression was associated with an odds ratio of 1.58 (1.31-1.89) P < .001; 1.24 (1.00-1.52), P = .046; and 1.89 (1.45-2.46), P < .001 for total falls, AFs and UFs, respectively, after controlling for relevant covariates. Participants with depression who fell were more likely to have prior falls, functional impairment and slower gait when compared with depressed participants who did not fall. DISCUSSION: The risk of falls associated with depression in older adults is more marked for UFs, with the association for AFs approaching borderline significance only. This finding is important because UFs require focused clinical assessment with attention to potential causes such as cardiac arrhythmia or orthostatic hypotension.