Disability Assessment For Dementia Research Articles

Effectiveness of the Interdisciplinary Home‐bAsed Reablement Program (I‐HARP) on improving functional independence of people living with dementia and process outcomes

AbstractBackgroundThis project evaluated a model of care integrating evidence‐based dementia rehabilitation strategies into a time‐limited, home‐based, interdisciplinary rehabilitation package: Interdisciplinary Home‐bAsed Reablement Program (I‐HARP). The aims were: to determine I‐HARP effectiveness on functional independence, mobility, quality of life and depression among people with dementia, their home environmental safety, carer burden and quality of life, and I‐HARP cost‐effectiveness; and to evaluate processes, outcomes and influencing factors of the I‐HARP implementation.MethodThe project was mixed‐methods action research combining a multi‐centre pragmatic RCT and realist evaluation. I‐HARP was a 4‐month model of care for community‐dwelling people with mild‐moderate dementia and family carers, incorporated into community aged care services and hospital‐based geriatric services in Sydney, Australia (2018‐22) and compared with usual care. Outcome assessments were conducted at baseline, 4‐ and 12‐month. Semi‐structured interviews with participants and focus groups with I‐HARP interventionists and participating site managers occurred post intervention. (ACTRN12618000600246)ResultOf 130 dyads of clients and their carers recruited, 116 dyads (58 per group) completed the trial (89% retention). The I‐HARP group had somewhat better mean results for most outcome measures than usual care at both 4 and 12 months, but the only statistically significant difference was a reduction in home environment hazards at 4 months. Post‐hoc sub‐group analysis of 66 clients with mild‐dementia found significantly better functional independence in the intervention group: 11.2 on Disability Assessment for Dementia (95% CI: 3.4,19.1; p = .005; ES 0.69) at 4 months and 13.7 (95% CI: 3.7,23.7; p = .007; ES 0.69) at 12 months. Preliminary results of economic evaluation pointed to potential benefits of I‐HARP over usual care. Interviews and focus group findings highlighted system and research design barriers (e.g., workforce, hospital system, communication, blinding and recruitment) and program facilitators (focus on enablement, interdisciplinary and teamwork).ConclusionThe I‐HARP model enhanced functional independence of participants with mild‐dementia but not in those with moderate‐dementia, so did not result in better outcomes in the group overall. A different type of rehabilitation model or strategies may be required as dementia becomes more severe. Key facilitators and barriers to I‐HARP implementation provide further insights to developing dementia rehabilitation model of care.

FC18: Can rehabilitation improve functional independence of older people with dementia? A pragmatic randomized controlled trial (RCT) of the Interdisciplinary Home-bAsed Reablement Program (I-HARP)

Objective:The Interdisciplinary Home-bAsed Reablement Program (I-HARP) integrates evidence-based rehabilitation strategies into a dementia-specific person-centred, time-limited, home-based, interdisciplinary rehabilitation package. I-HARP was a 4-month model of care, incorporated into community aged care services and hospital-based community geriatric services. I-HARP involved: 8-10 individually tailored home visits by occupational therapist and registered nurse; 2-4 optional other allied health sessions; up to A$1,000 minor home modifications and/or assistive devices; and three individual carer support sessions. The aim of the study was to determine the effectiveness of I-HARP on the health and wellbeing of people living with dementia and their family carers.Methods:A multi-centre pragmatic parallel-arm randomised controlled trial compared I-HARP to usual care in community-dwelling people with mild to moderate dementia and family carers in Sydney, Australia (2018-22). Assessments of the client’s daily activities, mobility and health-related quality of life, caregiver burden and quality of life were conducted at baseline, 4- and 12-month follow-up. Changes from baseline were compared between groups.Results:Of 260 recruited, 232 (116 dyads of clients and their carers, 58 dyads per group) completed the trial to 4-month follow-up (89% retention). Clients were: aged 60-97 years, 63% female, 57% with mild dementia and 43% with moderate dementia. The I-HARP group had somewhat better mean results for most outcome measures than usual care at both 4 and 12 months, but the only statistically significant difference was a reduction in home environment hazards at 4 months (reduction: 2.29 on Home Safety Self-Assessment Tool, 95% CI: 0.52, 4.08; p=.01, effect size [ES] 0.53). Post-hoc sub-group analysis of 66 clients with mild dementia found significantly better functional independence in the intervention group: 11.2 on Disability Assessment for Dementia (95% CI: 3.4, 19.1; p=.005; ES 0.69) at 4 months and 13.7 (95% CI: 3.7, 23.7; p=.007; ES 0.69) at 12 months.Conclusion:The I-HARP model enhanced functional independence of people with mild dementia only but not significantly in people with moderate dementia, so did not result in better outcomes in the group overall. A different type of rehabilitation model or strategies may be required as dementia becomes more severe.

Impact of study partner type on primary endpoint volatility in a phase 3 registration trial of mild‐to‐moderate Alzheimer’s disease

AbstractBackgroundIn Alzheimer’s disease (AD) clinical trials, participants are required to enroll with a study partner (SP) who ensures compliance and completes outcomes assessing participant cognitive and functional ability. The SP role is commonly filled by spouses and other family members. Spouse and non‐spouse SPs differ in numerous ways, including average time in contact with the participant. These differences may impact volatility of SP‐reported assessments, which may in turn impact trial integrity. We quantified the impact of SP type on the variance of SP‐reported Disability Assessment for Dementia (DAD) scores.MethodWe analyzed data from the Bapineuzumab 301 (ApoE e4 non‐carriers) and 302 (ApoE e4 carriers) phase 3 trials in mild‐to‐moderate AD, provided by the trial sponsor, Janssen Research & Development, LLC for use in these analyses. We compared the sample variances of end‐of‐study DAD scores for spousal and non‐spousal SPs in each trial. 95% confidence intervals (CIs) for the corresponding parameters were computed via bootstrapping. We used similar methods to compare the variances in the difference between baseline and end‐of‐study DAD scores for SP types.ResultAmong the 1,232 and 1,121 participants analyzed from trials 301 and 302, 818 (66.4%) and 837 (74.7%) had spousal SPs at baseline, respectively (Table 1). On the other hand, 665 (665/973 = 68.3%) and 697 (697/924 = 75.4%) spousal SPs in each trial completed the end‐of‐study visit, respectively. In trial 301, the variance of end‐of‐study DAD scores for spousal SPs were observed to be 14% lower compared to non‐spousal SPs (spousal/non‐spousal = 630.41/746.55 = 0.84, 95% CI = [0.71, 1.03]). In trial 302 this relative decrease was observed to be 9%, though with less precision (spousal /non‐spousal = 610.85/673.86 = 0.91, 95%CI = [0.77, 1.12]). Neither trial had significant differences in spousal vs non‐spousal variances of the change‐from‐baseline DAD scores (Trial 301: spousal/non‐spousal = 378.10/425.17 = 0.91, 95%CI = [0.66, 1.22]; Trial 302: spousal/non‐spousal = 354.38/352.22 = 1.01, 95%CI = [0.77, 1.35]). DAD variance over time is depicted in Figure 1. Differences in the linear trend of DAD variance did not significantly differ between SP types in either trial (Trial 301 Est.: ‐1.74, 95%CI: [‐3.58, 0.23]; Trial 302 Est.: 0.94, 95%CI: [‐5.83, 4.31]).ConclusionSP type was not associated with variation in SP‐reported study endpoints in this study.

What is the impact of ongoing statin use on cognitive decline and dementia progression in older adults with mild-moderate Alzheimer disease?

In addition to the clear cardiovascular benefit, there has been renewed interest in the potential of statins in the prevention of cognitive impairment and dementia in older adults. However, whether ongoing statin use can delay cognitive decline or dementia progression in those with established Alzheimer dementia, is unclear. Using data from NILVAD, we analysed the association between ongoing statin use and cognitive decline (Alzheimer Disease Assessment Scale-Cognitive Subsection [ADAS-Cog])/dementia progression (Clinical Dementia Rating Scale [CDR-Sb]/Disability Assessment for Dementia [DAD]) over 18 months in older adults with mild-moderate AD. Additionally, we assessed the association between ongoing statin use and adverse events in mild-moderate AD. Over one-third (34.9%) of 510 older adults with mild-moderate AD (aged: 72.9 years; 61.9% female) used a statin for the 18-month study duration. Statin use was not associated with the rate of cognitive decline (β: -0.67; 95% CI: -1.71, 0.36, p = 0.20) or dementia progression (β: -0.34; 95% CI -0.71, 0.02; p = 0.07 for CDR-Sb/ β: -2.00; -5.70, 1.70; p = 0.29 for DAD). Further, ongoing statin use was not associated with adverse events, serious adverse events, unscheduled GP visits, or unscheduled hospitalisation. Ongoing statin use was not associated with cognitive decline or dementia progression in mild-moderate AD. Similarly, use was not associated with adverse events including abnormal liver function tests or falls. Whilst safe in those with AD, the current results suggest ongoing statin use does not delay cognitive decline or clinical progression in established AD.

Effectiveness and safety of monoclonal antibodies against amyloid-beta vis-à-vis placebo in mild or moderate Alzheimer's disease.

Currently, no consensus has been reached on the therapeutic implications of monoclonal antibodies against amyloid-beta (Aβ) in Alzheimer's disease (AD). This study aimed to examine the effectiveness and safety of monoclonal antibodies against Aβ as a whole and also to determine the superiority of individual antibodies vis-à-vis placebo in mild or moderate AD. Literature retrieval, article selection, and data abstraction were performed independently and in duplicate. Cognition and function were appraised by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Effect sizes are expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). Twenty-nine articles involving 108 drug-specific trials and 21,383 participants were eligible for synthesis. Of the four assessment scales, only CDR-SB was significantly reduced after using monoclonal antibodies against Aβ relative to placebo (SMD: -0.12; 95% CI: -0.2 to -0.03; p = 0.008). Egger's tests indicated a low likelihood of publication bias. At individual levels, bapineuzumab was associated with a significant increase in MMSE (SMD: 0.588; 95% CI: 0.226-0.95) and DAD (SMD: 0.919; 95% CI: 0.105-1.943), and a significant decrease in CDR-SB (SMD: -0.15; 95% CI: -0.282-0.018). Bapineuzumab can increase the significant risk of serious adverse events (OR: 1.281; 95% CI: 1.075-1.525). Our findings indicate that monoclonal antibodies against Aβ can effectively improve instrumental activities of daily life in mild or moderate AD. In particular, bapineuzumab can improve cognition and function, as well as activities of daily life, and meanwhile, it triggers serious adverse events.

Retention of Participant and Study Partner Dyads in Alzheimer’s Disease Clinical Trials

AbstractBackgroundStudy retention is crucial to clinical trial success. Greater than expected dropout rates can lead to reduced power and biased results. Alzheimer’s disease (AD) trial success depends not only on participants but also on their study partners. We investigated whether study partner type was associated with the risk of dropout in large Phase 3 registration trials.MethodWe used data from two trials of bapineuzumab for patients with mild‐to‐moderate AD. Data were provided by the sponsor of the trials, Janssen Research & Development, LLC for use in these analyses. The co‐primary endpoints were the change from baseline to week 78 in the Disability Assessment for Dementia (DAD) and the 11‐item AD Assessment Scale (ADAS Cog‐11). We defined completers as participants with baseline and week 78 scores on ADAS Cog‐11 or DAD. Participants were excluded from our analyses if they did not declare a study partner type in the Resource Utilization in Dementia‐Lite (RUD‐Lite) or if they were missing ADAS Cog‐11 and DAD at baseline. Time‐to‐dropout was defined as the time from study enrollment to the time of the last visit during which ADAS Cog‐11 or DAD were conducted.ResultData were available for 1,234 participants in the non‐carrier study and 1,221 participants in the carrier study. Table 1 presents baseline characteristics for participants included in our analysis (n = 1,229 non‐carriers and n = 1,097 carriers). In both trials, we observed a higher proportion of participants enrolled with a spouse (non‐carriers: 817, 66.3%; carriers: 837, 76.3%). Approximately 75% of spousal dyads completed the non‐carrier trial, while 60% of adult‐child dyads and 54% of dyads with other study partners completed the trial. Differences in the proportion of completers were lower in the carrier study, with approximately 75%, 73%, and 70% of completers among spousal, adult child, and “other” dyads. The same trend for time‐to‐dropout can be seen in Figure 1.ConclusionWe found that a higher proportion of spousal dyads completed the trials compared to other dyad types. Understanding the factors driving these associations may help understand reasons for dropout and could lead to the development of retention strategies.

Impact of anticoagulation therapy on the cognitive decline and dementia in patients with non-valvular atrial fibrillation (cognitive decline and dementia in patients with non-valvular atrial fibrillation [CAF] trial).

Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials. The cognitive decline and dementia in patients with non-valvular atrial fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24months. A total of 101 patients were enrolled [mean age:73.7 ± 6.0 years, male: 54(53.5%)]. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41 ± 0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer's Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies. Use of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable. The results of this Vanguard study did not support the pursuit of a larger formally powered study.

Contributions of Caregiver Management Styles to the Discrepancy Between Reported and Observed Task Performance in People with Dementia.

The identification and understanding of the discrepancy between caregivers' reports of people with dementia's (PwD) performance of activities of daily living (ADLs) and observed performance, could clarify what kind of support a PwD effectively needs when completing tasks. Strategies used by caregivers have not been included in the investigation of this discrepancy. To (1) investigate if caregivers' report of PwD's ADL performance are consistent with PwD's observed performance; (2) explore if caregiver management styles, depression, and anxiety, contribute to this discrepancy. PwD (n = 64) were assessed with standardized performance-based (Assessment of Motor and Process Skills, AMPS) and informant-based (Disability Assessment for Dementia, DAD) ADL assessments. Caregivers completed depression (PHQ-9), anxiety (GAD-7), and dementia management style (DMSS: criticism, active-management, and encouragement) questionnaires. Cohen's kappa determined agreement/disagreement in ADL performance. To investigate the potential discrepancy between the DAD and AMPS, a continuous variable was generated: comparative ADL score. Multiple linear regression analysis explored whether caregivers' management styles, depression or anxiety could explain the ADL discrepancy. Poor level of agreement between observed and reported ADL performance [k = -0.025 (95% CI -0.123 -0.073)] was identified, with most caregivers underestimating ADL performance. The combined model explained 18% (R2 = 0.18, F(5,55) = 2.52, p≤0.05) of the variance of the comparative ADL score. Active-management (β= -0.037, t(60) = -3.363, p = 0.001) and encouragement (β= 0.025, t(60) = 2.018, p = 0.05) styles made the largest and statistically significant contribution to the model. Encouragement style could be advised for caregivers who underestimate ADL performance, while active management style for those who overestimate it. Findings have scope to increase caregivers' abilities to support PwD activity engagement in daily life.

Longitudinal effect of dementia carers' sense of coherence on burden.

A sense of coherence (SOC) could help us better understand why there are individuals who cope better than others in similar situations. The study aimed to assess the effect of SOC on the course of burden reports in relatives of persons with dementia. This was a prospective cohort study of 156 dementia carers. The SOC was assessed by the Orientation to Life Questionnaire (OLQ-13), burden by Burden Interview, and personal and contextual characteristics were collected via ad hoc questions. The main dementia symptoms, including functional difficulties (Disability Assessment for Dementia), neuropsychiatric symptoms (Neuropsychiatric Inventory), and cognitive impairment (Mini-Mental State Examination), were also assessed. A general linear model was adjusted to determine the effect of SOC and other covariates on burden throughout the follow-up. Burden differences between baseline and 12 and 24months were analysed, and the baseline OLQ-13 score was grouped by quartiles. The global burden reported increased after 24months (F=9.98; df=2; p<0.001), but not equally for all carers; daughters reported the greatest increase. SOC, functional disability, and neuropsychiatric disorders showed a significant effect on burden, but time did not. Carers with higher SOC at baseline tend to remain with lower burden levels, whereas carers with low SOC reported higher burden at each visit. This study reports evidence of the effect of SOC on burden at baseline, 12 and 24months of follow-up. Burden scores differ by carers' SOC; those with higher SOC showed lower burden levels, whereas the low-SOC group reported a greater burden at each visit.

Decreased 5-HT1A binding in mild Alzheimer's disease-A positron emission tomography study.

Decreased 5‐HT1A receptor binding has been associated with Alzheimer's disease (AD) and interpreted as a consequence of neuron loss. The purpose of the present study was to compare [11C]WAY100635 binding to the 5‐HT1A receptor in the hippocampus, entorhinal cortex, amygdala and pericalcarine cortex in mild AD patients and elderly controls. AD patients (n = 7) and elderly control subjects (n = 8) were examined with positron emission tomography (PET) and [11C]WAY100635. PET data acquisition was performed with an ECAT EXACT HR system. Wavelet‐aided parametric images of nondisplaceable binding potential (BP ND) were generated using Logan's graphical analysis with cerebellum as the reference region. Correction for partial volume effects was performed with the Müller–Gärtner method. Regions of interest (ROIs) were applied to the individual parametric images, and the regional BP ND was calculated as the average parametric voxel value within each ROI. In addition to comparisons between subject groups, correlations between BP ND values and scores on the Mini‐Mental State Examination, Disability Assessment for Dementia (DAD), and Neuropsychiatric Inventory were expressed by Pearson correlation coefficients. Mean regional BP ND was lower in AD patients than in control subjects, and the difference was statistically significant for the hippocampus, entorhinal cortex, and amygdala. A statistically significant correlation was obtained between hippocampal BP ND values and DAD scores. The results of the present study corroborate and extend previous findings of decreased 5‐HT1A binding in AD and strengthen the support for 5‐HT1A receptor PET as a tool for the assessment of neurodegenerative changes in mild AD.

A comparison of two approaches for modeling dementia progression in a changing patient context.

ObjectivesTo explain the heterogeneity in dementia disease trajectory, we studied the influence of changing patient characteristics on disease course by comparing the association of dementia progression with baseline comorbidity and frailty, and with time‐varying comorbidity and frailty.MethodsWe used individual growth models to study baseline and time‐varying associations in newly diagnosed dementia patients (n = 331) followed for 3 years. We measured cognition using the Mini‐Mental State Examination (MMSE), daily functioning using the Disability Assessment for Dementia (DAD), frailty using the Fried criteria and comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS‐G).ResultsAlthough baseline comorbidity and frailty were associated with decreased daily functioning at diagnosis, their effects clearly diminished over time. In contrast, when incorporating comorbidity and frailty as time‐varying covariates, comorbidity was associated with lower daily functioning, and frailty with both lower cognition and daily functioning. Being frail was associated with a 0.9‐point lower MMSE score (p = 0.03) and a 14.9‐point lower DAD score (p < 0.01). A 1‐point increase in CIRS‐G score was associated with a 1.1‐point lower DAD score (p < 0.01).ConclusionsTime‐varying comorbidity and frailty were more consistently associated with dementia disease course than baseline comorbidity and frailty. Therefore, modeling only baseline predictors is insufficient for understanding the course of dementia in a changing patient context.

Acute response to cholinergic challenge predicts long‐term response to galantamine treatment in patients with Alzheimer's disease

AimsCholinesterase inhibitors (CEIs) have been shown to improve cognitive functioning in Alzheimer's disease (AD) patients, but are associated with multiple side effects and only 20–40% of the patients clinically improve. In this study, we aimed to investigate the acute pharmacodynamic (PD) effects of administration of a single dose of galantamine on central nervous system (CNS) functioning in mild to moderate AD patients and its potential to predict long‐term treatment response.MethodsThis study consisted of a challenge and treatment phase. In the challenge phase, a single dose of 16 mg galantamine was administered to 50 mild to moderate AD patients in a double‐blind, placebo‐controlled cross‐over fashion. Acute PD effects were monitored up to 5 hours after administration with use of the NeuroCart CNS test battery and safety and pharmacokinetics were assessed. In the treatment phase, patients were treated with open‐label galantamine according to regular clinical care. After 6 months of galantamine treatment, patients were categorized as either responder or as non‐responder based on their minimental state examination (MMSE), neuropsychiatric inventory (NPI) and disability assessment in dementia (DAD) scores. An analysis of covariance was performed to study the difference in acute PD effects during the challenge phase between responders and non‐responders.ResultsA single dose of galantamine significantly reduced saccadic reaction time (−0.0099; 95% CI = −0.0195, −0.0003; P = .0430), absolute frontal EEG parameters in alpha (−14.9; 95% CI = −21.0, −8.3; P = .0002), beta (−12.6; 95% CI = −19.4, −5.3; P = .0019) and theta (−17.9; 95% CI = −25.0, −10.0; P = .0001) frequencies. Relative frontal (−1.669; 95% CI = −2.999, −0.339; P = .0156) and occipital (−1.856; 95% CI = −3.339, −0.372; P = .0166) EEG power in theta frequency and relative occipital EEG power in the gamma frequency (1.316; 95% CI = 0.158, 2.475; P = .0273) also increased significantly compared to placebo. Acute decreases of absolute frontal alpha (−20.4; 95% CI = −31.6, −7.47; P = .0046), beta (−15.7; 95% CI = −28.3, −0.93; P = .0390) and theta (−25.9; 95% CI = −38.4, −10.9; P = .0024) EEG parameters and of relative frontal theta power (−3.27%; 95% CI = −5.96, −0.58; P = .0187) on EEG significantly distinguished responders (n = 11) from non‐responders (n = 32) after 6 months.ConclusionsThis study demonstrates that acute PD effects after single dose of galantamine are correlated with long‐term treatment effects and that patients who demonstrate a reduction in EEG power in the alpha and theta frequency after a single administration of galantamine 16 mg will most likely respond to treatment.

Clinical use of deep speech parameters derived from the semantic verbal fluency task

AbstractBackgroundPrevious research showed that semantic memory is a good indicator for cognitive decline in early phases of Alzheimer’s disease. Automatically derived deep speech parameters from the semantic verbal fluency (SVF) can potentially have an additional value to differentiate SCI, MCI and dementia, compared to the total fluency score. However, the added diagnostic value of (specific) deep speech parameters to the commonly clinically used SVF raw score remains unknown. In the Deepspa project, we investigated the (additional) value of automatically derived speech parameters in clinical practice. We also investigated the relation between automatically derived speech parameters of the SVF and other cognitive tasks, as well as disease severity and functioning in daily living.MethodIn the DeepSPA project, 140 participants were recruited from the memory clinic of the MUMC+ (SCI, MCI, ADD). All subjects underwent a cognitive assessment including the SVF. The SVF (animals, 60 seconds) was administered by use of the Delta application (ki elements). Disease severity and functioning in daily life were administered by the Clinical Dementia Rating Scale (CDR) and Disability Assessment for Dementia (DAD) respectively. The agreement between the automatic and clinical raw score of the SVF was assessed by the interclass correlation coefficient. The relation between the deep speech parameters, such as mean word frequency, temporal and semantic clusters, transition time between words etc., and syndrome diagnosis, DAD and CDR were investigated using stepwise regression analyses, corrected for age, education level and gender.ResultPreliminary results showed that deep speech parameters have an additional value in the classification of clinical diagnosis, and disease severity. More specifically, mean word frequency and the mean time between temporal clusters had an added value. The reliability between word count by the application and the clinician was good (ICC=.882, 95% CI = .820‐.923). Results about the relation between deep speech parameters and other cognitive performances will be available at the conference.ConclusionFirst results suggest that deep speech parameters have an additional value in the early diagnostics of cognitive impairments. More information about the value of these non‐invasive automatically derived deep speech parameters could improve diagnostic accuracy in clinical practice.

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

Background:Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown.Objective:To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial.Methods:Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes.Results:Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082).Conclusion:This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.

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

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. 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. 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 (β: 3.53, 0.91-6.17, p=0.008) and 18 months (β: 3.81, 0.49-7.14, p=0.024) in addition to greater dementia progression at both 12 (β: 1.85, -0.97-2.73, p<0.001 for CDR-Sb/β: -3.33, -5.56-1.10, p=0.003 for DAD) and 18 months (β: 1.41, 0.16-2.67, p=0.027 for CDR-Sb/β: -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. 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.

Concurrent Validity of the ABC Dementia Scale with Other Standard Scales: A New Comprehensive Instrument for Assessing Dementia in Japan

Background/Aims: The ABC Dementia Scale (ABC-DS), a new tool for evaluating dementia, was developed in Japan. The ABC-DS is a comprehensive instrument that can simultaneously evaluate activities of daily living (ADLs), behavioral and psychological symptoms of dementia (BPSD), and cognitive function. The ABC-DS can be administered easily and quickly and can clarify the severity of dementia and its changes over time. While the ABC-DS has been reported to be useful in Alzheimer disease (AD)-type dementia, it has not yet been studied in other types of dementia. The purpose of this study was to reevaluate the standard validity of ABC-DS separately for various dementia types and severities. Methods: We evaluated the ABC-DS in outpatients at 1 hospital in Nagasaki Prefecture and patients who use the facility. Domain A, corresponding to ADLs, correlated with Disability Assessment for Dementia (DAD); domain B, corresponding to BPSD, correlated with the Neuropsychiatric Inventory (NPI); domain C, corresponding to cognitive functions, correlated with Mini-Mental State Examination (MMSE); and the total score of the ABC-DS correlated with the Clinical Dementia Rating (CDR). Results: 102 patients, comprising 38 males and 64 females with an average age of 80.7 ± 8.6 years, were enrolled. AD-type dementia was present in 38 cases, vascular dementia (VaD) in 23, mixed dementia in 23, dementia with Lewy bodies in 6, argyrophilic grain dementia in 9, and mild cognitive impairment in 3. A strong correlation was found between ABC-DS domain scores and their respective reference neuropsychological instruments (domain A and the DAD, domain B and the NPI, domain C and the MMSE, and total score and CDR). The correlation of each ABC-DS domain score with the corresponding standard scale depended on the type and severity of dementia, and we observed moderate or high correlations in AD and VaD patients with moderate and severe dementia. Discussion: Although the ABC-DS targets AD, it can be used in VaD based on the results of this study. In other types of dementia, the results differed depending on the domain; in some conditions, the ABC-DS may not show sufficient concurrent validity with other standard scales. Also, the ABC-DS is more beneficial for moderate-to-severe dementia, as reported in previous studies. It is highly useful in clinical practice in Japan since there more than half of all patients have moderate-to-severe dementia.

Cognitive Stimulation Therapy for Older Adults With Mild-to-Moderate Dementia in Italy: Effects on Cognitive Functioning, and on Emotional and Neuropsychiatric Symptoms.

Cognitive Stimulation Therapy (CST) is one of the most popular evidence-based interventions for people with dementia. The aim of the present study was to assess the effectiveness in the short- and long-term (on completing the treatment and 3 months later) of an Italian adaptation of the CST protocol (CST-IT). Older adults with mild-to-moderate dementia at 16 residential care homes were randomly assigned to a CST-IT group (N = 123) or an active control group (N = 102). The following domains were examined for potential benefits: general cognitive functioning (Mini-Mental State Examination [MMSE] and the Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog]), language (Narrative Language Test), mood and behavior (Cornell scale and Neuropsychiatric Inventory), everyday life functioning (Disability Assessment for Dementia), and quality of life (Quality of Life-Alzheimer's Disease scale). At both the short- and long-term assessments, the CST-IT group's MMSE scores remained stable, while the control group's scores decreased slightly from pretest to posttest and at follow-up. The CST-IT group also had short-term benefits in other cognitive measures (ADAS-Cog and Narrative Language Test) and mood and behavior measures, which were generally maintained at follow-up. No other differences were observed. The effectiveness of CST in sustaining cognitive and emotional functioning, and counteracting the progression of behavioral/neuropsychiatric symptoms in people with dementia was confirmed, and a long-term benefit was demonstrated. CST is a promising option for the treatment of people with dementia in clinical practice.

Pronounced Impairment of Activities of Daily Living in Posterior Cortical Atrophy

Introduction: The impact of several dementia syndromes on activities of daily living (ADLs) has been well documented, but no study has yet investigated functional ability in posterior cortical atrophy (PCA). The primarily visual nature of deficits in this condition is likely to have a pronounced impact on ADLs. Objective: The aim of this study was to profile functional change in PCA and identify predictors of change. Method: Twenty-nine PCA patients and 25 patients with typical Alzheimer’s disease (AD) and their caregivers were included in this cross-sectional study. ADLs were assessed using the Disability Assessment for Dementia (DAD), administered to caregivers, assessing basic ADLs (e.g., eating, dressing) and instrumental ADLs (e.g., managing finances, meal preparation). The predictive utility of cognitive domains (Addenbrooke’s Cognitive Examination), behavioural impairment (Cambridge Behavioural Inventory-Revised) and demographic variables on ADL ability was also examined. Results: PCA patients showed significantly reduced total ADL scores compared to AD patients (medium effect size, d = –0.7; p < 0.05), with significantly more impairment on basic ADLs (large effect size, d = –0.8; p < 0.05) but similar impairment on instrumental ADLs (medium effect size, d = –0.5; p > 0.05). A model combining patient mood, disinhibition, apathy, symptom duration, and memory and attention/orientation scores explained the variance of scores in functional decline (61.2%), but the key factor predicting ADL scores was attention/orientation (p = 0.048). Conclusion: This study shows the profound impact of PCA on ADLs and factors underpinning patients’ disability. Attention/orientation deficits were found to correlate and contribute to variance in ADL scores. Future work to develop tailored interventions to manage ADL impairment in PCA should take these findings into account.

Correlation between functionality, mobility and risk of falls in elderly people with Alzheimer’s disease

Abstract To evaluate functional capacity, mobility and balance in elderly patients with Alzheimer's Disease (AD), in its mild, moderate and severe forms, verifying the existence of correlation among these parameters. Eighty-eight elderly patients (81.79 ± 6.54 years) diagnosed with AD treated at an elderly care reference center in Taguatinga-DF were selected, and information was collected between November 2018 and March 2019. Data collection was initially made by filling in the evaluation form. Subsequently, two questionnaires were administered to caregivers (Clinical Dementia Rating-CDR and Disability Assessment for Dementia -DAD) and two tests to demented patients (Southampton Assessment of Mobility-SAM-Br and Timed Up and Go-TUG). Variables were correlated using the SPSS software version 22 using Pearson's correlation, with significance level p?0.05. The following results were obtained: 1. weak correlations between CDR and DAD (p = 0.04; r = -0.31) with significant difference; 2. strong correlation and significant difference between CDR and TUG (p = 0.02; r = 0.87); 3. weak and non-significant correlation between CDR and SAM-Br (p = 0.14; r = -0.24); 4. significant difference and highly strong correlation between SAM-Br and TUG (p = 0.01; r = 0.70). Older adults with Alzheimer's disease present decreased functional capacity, mobility and risk of falls associated with the disease progression. SAM-Br and TUG tools showed strong correlation and, although it is a generic measure, TUG showed strong correlation with AD progression, and may be a predictive test for the risk of falls in this population.

Prediction of poor clinical outcome in vascular cognitive impairment: TRACE-VCI study.

IntroductionPrognostication in memory clinic patients with vascular brain injury (eg possible vascular cognitive impairment [VCI]) is often uncertain. We created a risk score to predict poor clinical outcome.MethodsUsing data from two longitudinal cohorts of memory clinic patients with vascular brain injury without advanced dementia, we created (n = 707) and validated (n = 235) the risk score. Poor clinical outcome was defined as substantial cognitive decline (change of Clinical Dementia Rating ≥1 or institutionalization) or major vascular events or death. Twenty‐four candidate predictors were evaluated using Cox proportional hazard models.ResultsAge, clinical syndrome diagnosis, Disability Assessment for Dementia, Neuropsychiatric Inventory, and medial temporal lobe atrophy most strongly predicted poor outcome and constituted the risk score (C‐statistic 0.71; validation cohort 0.78). Of note, none of the vascular predictors were retained in this model. The 2‐year risk of poor outcome was 6.5% for the lowest (0‐5) and 55.4% for the highest sum scores (10‐13).DiscussionThis is the first, validated, prediction score for 2‐year clinical outcome of patients with possible VCI.