Feasibility study of assessing the Preclinical Alzheimer Cognitive Composite (PACC) score via videoconferencing.
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ABSTRACT: Background
The Preclinical Alzheimer Cognitive Composite (PACC) is a composite score which can detect the first signs of cognitive impairment, which can be of importance for research and clinical practice. It is designed to be administered in person; however, in-person assessments are costly, and are difficult during the current COVID-19 pandemic.Objective
To assess the feasibility of performing the PACC assessment with videoconferencing, and to compare the validity of this remote PACC with the in-person PACC obtained previously.Methods
Participants from the HEalth and Ageing Data IN the Game of football (HEADING) Study who had already undergone an in-person assessment were re-contacted and re-assessed remotely. The correlation between the two PACC scores was estimated. The difference between the two PACC scores was calculated and used in multiple linear regression to assess which variables were associated with a difference in PACC scores.Findings
Of the 43 participants who were invited to this external study, 28 were re-assessed. The median duration in days between the in-person and the remote assessments was 236.5 days (7.9 months) (IQR 62.5). There was a strong positive correlation between the two assessments for the PACC score, with a Pearson correlation coefficient of 0·82 (95% CI 0·66, 0·98). The multiple linear regression found that the only predictor of the PACC difference was the time between assessments.Interpretation
This study provides evidence on the feasibility of performing cognitive tests online, with the PACC tests being successfully administered through videoconferencing. This is relevant, especially during times when face-to-face assessments cannot be performed.
SUBMITTER: Seghezzo G
PROVIDER: S-EPMC7836343 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes.To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evidence of AD pathology using the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess episodic memory, timed executive function, and global cognition. The ADCS-PACC is the primary outcome measure for the first clinical trial in preclinical AD (ie, the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study).With the ADCS-PACC, we derive pilot estimates of amyloid-related decline using data from 2 observational studies conducted in North America and another conducted in Australia. The participants analyzed had normal cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies.For the 2 studies that collected data on A? levels (ADNI and AIBL), we estimate decline in a preclinical AD "A?-positive" placebo group and compare them with an "A?-negative" group. For the study that did not include data on A? levels (the ADCS Prevention Instrument [ADCS-PI] study), we grouped participants by the presence of APOE-?4 and by clinical progression.In ADNI, A?-positive participants showed more decline than did A?-negative participants with regard to the ADCS-PACC score at 24 months (mean [SE] difference, -1.239 [0.522] [95% CI, -2.263 to -0.215]; P?=?.02). In AIBL, the mean (SE) difference is significant at both 18 months (-1.009 [0.406] [95% CI, -1.805 to -0.213]; P?=?.01) and 36 months (-1.404 [0.452] [95% CI, -2.290 to -0.519]; P?=?.002). In the ADCS-PI study, APOE-?4 allele carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE] score, -0.742 [0.294] [95% CI, -1.318 to -0.165]; P?=?.01) and 36 months (-1.531 [0.469] [95% CI, -2.450 to -0.612]; P?=?.001). In the ADCS-PI study, cognitively normal participants who progress from a global Clinical Dementia Rating score of 0 are significantly worse on the ADCS-PACC than cognitively normal participants who are stable with a global Clinical Dementia Rating score of 0 at months 12, 24, and 36 (mean [SE] ADCS-PACC score, -4.471 [0.702] [95% CI, -5.848 to -3.094]; P?<?.001). Using pilot estimates of variance and assuming 500 participants per group with 30% attrition and a 5% ? level, we project 80% power to detect effects in the range of ??=?0.467 to 0.733 on the ADCS-PACC.Analyses of at-risk cognitively normal populations suggest that we can reliably measure the first signs of cognitive decline with the ADCS-PACC. These analyses also suggest the feasibility of secondary prevention trials.
| S-EPMC4439182 | biostudies-literature
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| S-EPMC5173327 | biostudies-literature
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| S-EPMC5496516 | biostudies-literature
Project description:ObjectiveTo examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metabolism in elderly cognitively healthy (HC) subjects with preclinical Alzheimer disease (AD).MethodsFifty-two HC subjects (mean age 75 years) with FDG-PET and CSF measurement of Aβ1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Aβ1-42 was <192 pg/mL (Aβ1-42 [+]) vs HC with normal Aβ (Aβ1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Aβ1-42 status (Aβ1-42 [+] vs Aβ1-42 [-]) on FDG-PET metabolism in regions of interest (ROIs) (posterior cingulate, angular gyrus, inferior/middle temporal gyrus) and the whole brain (voxel-based).ResultsAn interaction between education and CSF Aβ1-42 status was observed for FDG-PET in the posterior cingulate (p < 0.001) and angular gyrus ROIs (p = 0.03), but was not significant for the inferior/middle temporal gyrus ROI (p = 0.06), controlled for age, sex, and global cognitive ability (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the Aβ1-42 (+) group, but with higher FDG-PET in the Aβ1-42 (-) group. Voxel-based analysis showed that this interaction effect was primarily restricted to temporo-parietal and ventral prefrontal brain areas.ConclusionsHigher education was associated with lower FDG-PET in preclinical AD (Aβ1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism.
| S-EPMC3691784 | biostudies-literature
Project description:Mindfulness-based group therapy is a rapidly growing psychological approach that can potentially help people adjust to chronic illness and manage unpleasant symptoms. Emerging evidence suggests that mindfulness-based interventions may benefit people with Parkinson's. The objective of the paper is to examine the appropriateness, feasibility, and potential cost-effectiveness of an online mindfulness intervention, designed to reduce anxiety and depression for people with Parkinson's. We conducted a feasibility randomized control trial and qualitative interviews. Anxiety, depression, pain, insomnia, fatigue, impact on daily activities and health-related quality of life were measured at baseline, 4, 8, and 20 weeks. Semi-structured interviews were conducted at the end of the intervention. Participants were randomized to the Skype delivered mindfulness group (n = 30) or wait-list (n = 30). Participants in the mindfulness group were also given a mindfulness manual and a CD with mindfulness meditations. The intervention did not show any significant effects in the primary or secondary outcome measures. However, there was a significant increase in the quality of life measure. The incremental cost-effectiveness ratio was estimated to be £27,107 per Quality-Adjusted Life Year gained. Also, the qualitative study showed that mindfulness is a suitable and acceptable intervention. It appears feasible to run a trial delivering mindfulness through Skype, and people with Parkinson's found the sessions acceptable and helpful.
| S-EPMC8678660 | biostudies-literature
Project description:Recently, the focus of Alzheimer's disease (AD) research has shifted from the clinical stage to the preclinical stage. We, therefore, aimed to develop a cognitive composite score that can detect the subtle cognitive differences between the amyloid positive (A?+) and negative (A?-) status in cognitively normal (CN) participants. A total of 423 CN participants with A? positron emission tomography images were recruited. The multiple-indicators multiple-causes model found the latent mean difference between the A?+?and A?- groups in the domains of verbal memory, visual memory, and executive functions. The multivariate analysis of covariance (MANCOVA) showed that the A?+?group performed worse in tests related to the verbal and visual delayed recall, semantic verbal fluency, and inhibition of cognitive inference within the three cognitive domains. The Preclinical Amyloid Sensitive Composite (PASC) model we developed using the result of MANCOVA and the MMSE presented a good fit with the data. The accuracy of the PASC score when applied with age, sex, education, and APOE ?4 for distinguishing between A?+?and A?- was adequate (AUC?=?0.764; 95% CI?=?0.667-0.860) in the external validation set (N?=?179). We conclude that the PASC can eventually contribute to facilitating more prevention trials in preclinical AD.
| S-EPMC7423599 | biostudies-literature
Project description:ImportanceAlzheimer disease (AD) pathology starts with a prolonged phase of β-amyloid (Aβ) accumulation without symptoms. The duration of this phase differs greatly among individuals. While this disease phase has high relevance for clinical trial designs, it is currently unclear how to best predict the onset of clinical progression.ObjectiveTo evaluate combinations of different plasma biomarkers for predicting cognitive decline in Aβ-positive cognitively unimpaired (CU) individuals.Design, setting, and participantsThis prospective population-based prognostic study evaluated data from 2 prospective longitudinal cohort studies (the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention [WRAP]), with data collected from February 8, 2010, to October 21, 2020, for the BioFINDER-1 cohort and from August 11, 2011, to June 27, 2021, for the WRAP cohort. Participants were CU individuals recruited from memory clinics who had brain Aβ pathology defined by cerebrospinal fluid (CSF) Aβ42/40 in the BioFINDER-1 study and by Pittsburgh Compound B (PiB) positron emission tomography (PET) in the WRAP study. A total of 564 eligible Aβ-positive and Aβ-negative CU participants with available relevant data from the BioFINDER-1 and WRAP cohorts were included in the study; of those, 171 Aβ-positive participants were included in the main analyses.ExposuresBaseline P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, and neurofilament light measured in plasma; CSF biomarkers in the BioFINDER-1 cohort, and PiB PET uptake in the WRAP cohort.Main outcomes and measuresThe primary outcome was longitudinal measures of cognition (using the Mini-Mental State Examination [MMSE] and the modified Preclinical Alzheimer Cognitive Composite [mPACC]) over a median of 6 years (range, 2-10 years). The secondary outcome was conversion to AD dementia. Baseline biomarkers were used in linear regression models to predict rates of longitudinal cognitive change (calculated separately). Models were adjusted for age, sex, years of education, apolipoprotein E ε4 allele status, and baseline cognition. Multivariable models were compared based on model R2 coefficients and corrected Akaike information criterion.ResultsAmong 171 Aβ-positive CU participants included in the main analyses, 119 (mean [SD] age, 73.0 [5.4] years; 60.5% female) were from the BioFINDER-1 study, and 52 (mean [SD] age, 64.4 [4.6] years; 65.4% female) were from the WRAP study. In the BioFINDER-1 cohort, plasma P-tau217 was the best marker to predict cognitive decline in the mPACC (model R2 = 0.41) and the MMSE (model R2 = 0.34) and was superior to the covariates-only models (mPACC: R2 = 0.23; MMSE: R2 = 0.04; P < .001 for both comparisons). Results were validated in the WRAP cohort; for example, plasma P-tau217 was associated with mPACC slopes (R2 = 0.13 vs 0.01 in the covariates-only model; P = .01) and MMSE slopes (R2 = 0.29 vs 0.24 in the covariates-only model; P = .046). Sparse models were identified with plasma P-tau217 as a predictor of cognitive decline. Power calculations for enrichment in hypothetical clinical trials revealed large relative reductions in sample sizes when using plasma P-tau217 to enrich for CU individuals likely to experience cognitive decline over time.Conclusions and relevanceIn this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.
| S-EPMC10087054 | biostudies-literature
Project description:Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.Data from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage.The rate of annualized composite score decline was significantly greater for the high CERAD (p?<?0.001, d?=?0.56) and Braak (p?<?0.001, d?=?0.55) groups compared with the low CERAD and Braak groups, respectively. Mixed-model repeated measure (MMRM) analyses revealed a significantly greater difference in composite score change from baseline for the high CERAD group relative to the low CERAD group after 5 years (??=?-2.74, 95% confidence interval (CI) -5.01 to -0.47; p?=?0.02). A similar analysis between low and high Braak stage groups found no significant difference in change from baseline (??=?-0.69, 95% CI -3.03 to 1.66; p?=?0.56).These data provide evidence that decreased cognitive composite scores were significantly associated with increased AD pathology and provide support for the use of cognitive composite scores in AD prevention trials.
| S-EPMC6134796 | biostudies-other
Project description:IntroductionAmyloid-related decline in semantic memory was recently shown to be observable in the preclinical period of Alzheimer's disease. Cognitive composites designed to be sensitive to cognitive change in preclinical Alzheimer's disease (e.g., preclinical Alzheimer's cognitive composite [PACC]) and currently used in secondary prevention trials do not currently integrate measures of semantic processing. Our objective was to determine whether a standard semantic measure (i.e., category fluency [CAT] to animals, fruits, and vegetables) adds independent information above and beyond A?-related decline captured by the PACC.MethodsClinically normal older adults from the Harvard Aging Brain Study were identified at baseline as A?+ (n = 70) or A?- (n = 209) using Pittsburgh compound B-positron emission tomography imaging and followed annually with neuropsychological testing for 3.87 ± 1.09 years. The relationships between PACC, CAT, and variations of the PACC including/excluding CAT were examined using linear mixed models controlling for age, sex, and education. We additionally examined decline on CAT by further grouping A?+ participants into preclinical stage 1 and stage 2 on the basis of neurodegeneration markers.ResultsCAT explained unique variance in amyloid-related decline, with A?+'s continuing to decline relative to A?-'s in CAT even after controlling for overall PACC decline. In addition, removal of CAT from the PACC resulted in a longitudinal A?+/- effect size reduction of 20% at 3-year follow-up and 12% at 5-year follow-up. Finally, both stage 1 and stage 2 participants declined on CAT in comparison with stage 0, suggesting CAT declines early within the preclinical trajectory.ConclusionAddition of CAT to the PACC provides unique information about early cognitive decline not currently captured by the episodic memory, executive function, and global cognition components and may therefore improve detection of early A?-related cognitive decline.
| S-EPMC5726754 | biostudies-literature
Project description:IntroductionThe Alzheimer's Disease Composite Score (ADCOMS) is a tool developed to detect clinical progression and measure treatment effect in patients in early stages of Alzheimer's disease (AD). The psychometric properties of the ADCOMS have been established; however, the threshold for clinical meaningfulness has yet to be identified.MethodsAnchor-based, distribution-based, and ROC curve analyses were used to estimate clinically meaningful thresholds for change in ADCOMS for patients with mild cognitive impairment (MCI) and AD dementia. This study included data from three sources: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Alzheimer's Coordinating Center (NACC), and a legacy dataset that included data from four sources: the placebo group from three MCI trials and an earlier data cut from ADNI. Results were stratified by disease severity (MCI vs. dementia) and APOE ε4 carrier status.ResultsA total of 5355 participants were included in the analysis. The ADCOMS was able to detect change for MCI and dementia patients who experienced a meaningful decline in cognition (as defined by the Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB]) between baseline and month 12. The following ADCOMS cut-offs were proposed: 0.05 for MCI and 0.10 for dementia.ConclusionsThe ADCOMS was previously established as a valid and reliable tool for use in clinical trials for MCI due to AD and dementia populations. By defining thresholds for clinically meaningful change of ADCOMS, this work is an important step in interpreting clinical findings and estimates of treatment effects in early stage AD trials.
| S-EPMC9338189 | biostudies-literature