Development of a Simple Screening Tool for Determining Cognitive Status in Alzheimer’ Disease
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ORGANISM(S): Homo sapiens (human)
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PROVIDER: S-BSST951 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:ObjectiveThere remains a need for a non-invasive and cost-effective screening measure that could be administered prior to the provision of a lumbar puncture or positron emission tomography scan for the detection of preclinical Alzheimer disease (AD). Previous findings suggest that a hippocampally-based spatial navigation task may be effective for screening individuals for the preclinical AD continuum (i.e., low cerebrospinal fluid (CSF) Aβ42). Unfortunately, this task took 1.5-2 hours to administer, which would be time-prohibitive in a clinical setting. Therefore, the goal of this study was to compare psychometric properties of six spatial navigation-related tasks in order to take the next steps in developing a clinically appropriate screening measure.MethodsPsychometric properties (i.e., reliability, diagnostic accuracy, validity) of a modified version of the cognitive mapping task, two binding tasks, a visual perspective taking task, and self- and informant report versions of a questionnaire were examined in a sample of 91 clinically normal (CN) individuals. CSF Aβ42 and ptau181 were available for 30 individuals.ResultsThe learning phase of the cognitive mapping task and the self-report questionnaire were sensitive to identifying individuals in the preclinical AD continuum (93% and 87% sensitivity, 60% and 67% specificity, respectively). These two measures also demonstrated good test-retest stability (intraclass correlation coefficients = .719 and .838, respectively) and internal consistency (Cronbach's αs = .825 and .965, respectively).ConclusionsThese findings suggest that a self-report questionnaire and aspects of a cognitive mapping task may be particularly appropriate for development as screening tools for identifying individuals in the preclinical AD continuum.
| S-EPMC6849466 | biostudies-literature
Project description:ObjectiveTo determine the time required for a preclinical Alzheimer disease population to decline in a meaningful way, use estimates of decline to update previous clinical trial design assumptions, and identify factors that modify β-amyloid (Aβ)-related decline.MethodsIn 1,120 cognitively unimpaired individuals from 3 international cohorts, we estimated the relationship between Aβ status and longitudinal changes across multiple cognitive domains and assessed interactions between Aβ and baseline factors. Power analyses were performed to explore sample size as a function of treatment effect.ResultsCognitively unimpaired Aβ+ participants approach mild cognitive impairment (MCI) levels of performance 6 years after baseline, on average. Achieving 80% power in a simulated 4-year treatment trial, assuming a 25% treatment effect, required 2,000 participants/group. Multiple factors interacted with Aβ to predict cognitive decline; however, these findings were all cohort-specific. Despite design differences across the cohorts, with large sample sizes and sufficient follow-up time, the Aβ+ groups declined consistently on cognitive composite measures.ConclusionsA preclinical AD population declines to the cognitive performance of an early MCI population in 6 years. Slowing this rate of decline by 40%-50% delays clinically relevant impairment by 3 years-a potentially meaningful treatment effect. However, assuming a 40%-50% drug effect highlights the difficulties in preclinical AD trial design, as a more commonly assumed treatment effect of 25% results in a required sample size of 2,000/group. Designers of preclinical AD treatment trials need to prepare for larger and longer trials than are currently being considered. Interactions with Aβ status were inconsistent and not readily generalizable.
| S-EPMC6669933 | biostudies-literature
Project description:BACKGROUND:Loss and grief are experienced by caregivers of persons with dementia (PWD), relating to the ambiguous loss of PWD even when they are still alive and the anticipation of future loss related to their physical death. Such experience of caregiver grief is not easily recognized in clinical practice, despite its association with adverse effects such as caregiver burden, caregiver depression and caregivers' desire to place the PWD in nursing homes. We constructed a simple screening tool - based on factors associated with caregiver grief - to identify caregivers with high grief. METHODS:Spouses or children of community-dwelling PWD (n?=?403) completed self-administered questionnaires containing a well-established grief scale and information related to the caregiver and PWD. We split the study sample into two - the derivation sample (n?=?300) was used to identify factors associated with grief (using logistic regression) and derive a simple tool based on the number of identified factors; the validation sample (n?=?103) evaluated the performance of the tool using the receiver-operating-characteristic-curve-analysis (ROC). RESULTS:Four key factors were identified by the multivariable regression - more severe dementia (odds ratio, OR 6.9), behavioral problems in PWD (OR 5.0), spousal caregivers (OR 6.0) and daily caregiving (OR 3.0). The screening tool (based on the number of key factors) had an area under ROC of 0.77. At the optimal cut-off of ?2 key factors, the tool had a sensitivity of 0.91 and a specificity of 0.42. CONCLUSIONS:The identified factors are consistent with current understanding on caregiver grief. They can be easily integrated into the workflow of routine services to screen for caregivers who are more likely to benefit from further grief-related assessment.
| S-EPMC6391777 | biostudies-literature
Project description:Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) may influence brain reserve, the ability of the brain to tolerate pathological changes without significant decline in function. Here, we explore whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of Alzheimer disease (AD) and whether that response depends on an upregulation of the BDNF pathway. We observed increased neuronal TrkB expression associated with early-stage AD pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from cognitively intact Framingham Heart Study subjects (n = 5) when compared with cognitively intact individuals with no neurofibrillary tangles (n = 4). Because BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, we examined the expression of actin capping protein ?2 (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was also significantly increased in CA1 hippocampal neurons of cognitively intact subjects with early-stage AD pathology. Our data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and Capzb2 expression achieved may not be sufficient to prevent cognitive decline.
| S-EPMC3398703 | biostudies-literature
Project description:Background and objectivesSpasticity is common in long-term care facilities; however, this often-disabling condition is largely underdiagnosed in this setting and therefore left untreated. This study aimed to test the ability of a three-question flowchart used at the bedside by primary care providers in the long-term care setting to identify residents in need of referral to a specialist for spasticity consultation.MethodsAll residents of a single long-term care facility were approached for participation in this cross-sectional, observational study. Spasticity diagnostic evaluations by a movement disorders specialist neurologist (reference standard) were compared with referral determinations made by two primary care providers [a primary care physician (PCP) and a nurse practitioner (NP)] using the simple flowchart.ResultsThe analysis included 49 residents (80% male, age 78.2±9.0 years) who were evaluated by the reference standard neurologist and at least one primary care provider. The bedside referral tool demonstrated high sensitivity and moderate specificity when used by the PCP (92% and 78%, respectively; AUC=0.84) and NP (80% and 53%, respectively; AUC=0.67).ConclusionThis simple tool may be useful for primary care providers to identify residents to be referred to a specialist for evaluation and treatment of spasticity. These results warrant further investigation of the potential utility of this screening tool across multiple long-term care facilities and various types of care providers.
| S-EPMC7234972 | biostudies-literature
Project description:To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter.As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals.On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale.Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.
| S-EPMC2942032 | biostudies-literature
Project description:ImportanceAccurate blood-based biomarkers for Alzheimer disease (AD) might improve the diagnostic accuracy in primary care, referrals to memory clinics, and screenings for AD trials.ObjectiveTo examine the accuracy of plasma β-amyloid (Aβ) and tau measured using fully automated assays together with other blood-based biomarkers to detect cerebral Aβ.Design, setting, and participantsTwo prospective, cross-sectional, multicenter studies. Study participants were consecutively enrolled between July 6, 2009, and February 11, 2015 (cohort 1), and between January 29, 2000, and October 11, 2006 (cohort 2). Data were analyzed in 2018. The first cohort comprised 842 participants (513 cognitively unimpaired [CU], 265 with mild cognitive impairment [MCI], and 64 with AD dementia) from the Swedish BioFINDER study. The validation cohort comprised 237 participants (34 CU, 109 MCI, and 94 AD dementia) from a German biomarker study.Main outcome and measuresThe cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio was used as the reference standard for brain Aβ status. Plasma Aβ42, Aβ40 and tau were measured using Elecsys immunoassays (Roche Diagnostics) and examined as predictors of Aβ status in logistic regression models in cohort 1 and replicated in cohort 2. Plasma neurofilament light chain (NFL) and heavy chain (NFH) and APOE genotype were also examined in cohort 1.ResultsThe mean (SD) age of the 842 participants in cohort 1 was 72 (5.6) years, with a range of 59 to 88 years, and 446 (52.5%) were female. For the 237 in cohort 2, mean (SD) age was 66 (10) years with a range of 23 to 85 years, and 120 (50.6%) were female. In cohort 1, plasma Aβ42 and Aβ40 predicted Aβ status with an area under the receiver operating characteristic curve (AUC) of 0.80 (95% CI, 0.77-0.83). When adding APOE, the AUC increased significantly to 0.85 (95% CI, 0.82-0.88). Slight improvements were seen when adding plasma tau (AUC, 0.86; 95% CI, 0.83-0.88) or tau and NFL (AUC, 0.87; 95% CI, 0.84-0.89) to Aβ42, Aβ40 and APOE. The results were similar in CU and cognitively impaired participants, and in younger and older participants. Applying the plasma Aβ42 and Aβ40 model from cohort 1 in cohort 2 resulted in slightly higher AUC (0.86; 95% CI, 0.81-0.91), but plasma tau did not contribute. Using plasma Aβ42, Aβ40, and APOE in an AD trial screening scenario reduced positron emission tomography costs up to 30% to 50% depending on cutoff.Conclusions and relevancePlasma Aβ42 and Aβ40 measured using Elecsys immunoassays predict Aβ status in all stages of AD with similar accuracy in a validation cohort. Their accuracy can be further increased by analyzing APOE genotype. Potential future applications of these blood tests include prescreening of Aβ positivity in clinical AD trials to lower the costs and number of positron emission tomography scans or lumbar punctures.
| S-EPMC6593637 | biostudies-literature
Project description:To use large-scale network (LSN) analysis to classify subjects with Alzheimer disease (AD), those with amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) subjects.The study was conducted with institutional review board approval and was in compliance with HIPAA regulations. Written informed consent was obtained from each participant. Resting-state functional magnetic resonance (MR) imaging was used to acquire the voxelwise time series in 55 subjects with clinically diagnosed AD (n = 20), aMCI (n =15), and normal cognitive function (n = 20). The brains were divided into 116 regions of interest (ROIs). The Pearson product moment correlation coefficients of pairwise ROIs were used to classify these subjects. Error estimation of the classifications was performed with the leave-one-out cross-validation method. Linear regression analysis was performed to analyze the relationship between changes in network connectivity strengths and behavioral scores.The area under the receiver operating characteristic curve (AUC) yielded 87% classification power, 85% sensitivity, and 80% specificity between the AD group and the non-AD group (subjects with aMCI and CN subjects) in the first-step classification. For differentiation between subjects with aMCI and CN subjects, AUC was 95%; sensitivity, 93%; and specificity, 90%. The decreased network indexes were significantly correlated with the Mini-Mental State Examination score in all tested subjects. Similarly, changes in network indexes significantly correlated with Rey Auditory Verbal Leaning Test delayed recall scores in subjects with aMCI and CN subjects.LSN analysis revealed that interconnectivity patterns of brain regions can be used to classify subjects with AD, those with aMCI, and CN subjects. In addition, the altered connectivity networks were significantly correlated with the results of cognitive tests.
| S-EPMC3064820 | biostudies-other
Project description:Understanding the mechanisms involved in cognitive resilience in Alzheimer’s disease (AD) represents a promising strategy to identify novel treatments for dementia in AD. Previous findings from our group revealed that the study of aged-Tg2576 cognitive resilient individuals is a suitable tool for this purpose. Here, by performing a transcriptomic analysis of the prefrontal cortex of demented and resilient Tg2576 mice, we have been able to hypothesize that pathways involved in inflammation, amyloid degradation, memory function and neurotransmission may be playing a role on cognitive resilience in AD. Intriguingly, the results obtained in this study are suggestive of a reduction of the influx of peripheral immune cells into the brain on cognitive resilient subjects. Indeed, Cd4 mRNA expression is significantly reduced on Tg2576 mice with cognitive resilience and interestingly, we have found a negative correlation between CD4 mRNA levels in the periphery and the score in the Mini-Mental State Exam of AD patients. All of this, highlights the importance of understanding the role of the immune system on the development of neurodegenerative diseases and points out to the infiltration of CD4+ cells in the brain as a key player of cognitive dysfunction in AD.
2023-09-19 | GSE180968 | GEO
Project description:BACKGROUND:The goal of the present study was to analyze the macular microvacular network in mild cognitive impirment (MCI) and Alzheimer disease (AD). METHODS:Twelve patients with AD and 19 patients with MCI were recruited together with 21 cognitively normal controls with a similar range of ages. Optical coherence tomography angiography was used to image the retinal microvascular network at the macular region, including retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP). Fractal analysis (box counting, Dbox) representing the microvascular density was performed in different annular zones and quadrantal sectors. The macular ganglion cell-inner plexiform layer (GC-IPL) thickness was measured using Zeiss OCT. The relationship between the retinal microvasculature and clinical manifestations was analyzed. RESULTS:Patients with AD had lower densities of RVN, SVP, and DVP in the annulus, from 0.6 to 2.5 mm in diameter (P < 0.05) in comparison with controls. Patients with MCI had lower density of DVP in the superior nasal quadrant (P < 0.05) than that of the controls. There were no significant differences of GC-IPL thickness among groups (P > 0.05). There was a trend of vascular density loss from control to MCI then AD (P < 0.05). Retinal microvascular density of DVP was correlated with GC-IPL thickness (P < 0.05) in patients with AD, but not in patients with MCI and controls. CONCLUSIONS:Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD.
| S-EPMC5902666 | biostudies-other