Search

Background and purpose: The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults. Methods: Cross‐sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini‐Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders. Results: Across all studies, 23,819 participants aged 55–104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from −0.19 to −1.17 in NACC, −0.03 to −2.27 in MAP and −0.04 to −0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia). Conclusions: Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults. [ABSTRACT FROM AUTHOR]

Background: Developing effective strategies for reducing dementia risk requires a detailed understanding of the risk and protective factors associated with the progression of mild cognitive impairment (MCI) to dementia. Objective: We aimed to systematically review the evidence for sex differences in these factors. Methods: Five online databases (PubMed/CINAHL/EMBASE/PsycINFO/Cochrane) were searched from inception until 17 October 2022 for cohort studies that focused on sex differences in risk and protective factors in the progression of MCI to dementia. Results: A total of 2,972 studies were identified, of which 12 studies from five countries were included in the systematic review. There was substantial variability in study designs, study populations and outcome measures. Sex differences were present in the associations of sociodemographic, health, psychological factors, genetic and other biomarkers with the progression of MCI to dementia. APOE ɛ4 status and depression appeared to increase the risk of progression for females, whereas history of stroke, MRI markers and cerebrospinal fluid biomarkers appeared to increase the risk of progression for males. APOE ɛ2 status and marital status (unmarried) were observed to reduce risk of progression in males and females, respectively. Conclusions: The ability of studies to accurately detail risk factors for dementia are likely limited when solely controlling for the effects of sex. Although the heterogeneity and underpowered nature of the studies made it difficult to synthesize the findings for each risk factor, this study highlights the apparent need for further research examining risk factors for dementia in males and females with MCI separately. [ABSTRACT FROM AUTHOR]

Objective: To optimise dementia prevention strategies, we must understand the complex relationships between lifestyle behaviours, frailty and genetics.Methods: We explored relationships between frailty index, healthy lifestyle and polygenic risk scores (all assessed at study entry) and incident all-cause dementia as recorded on hospital admission records and death register data.Results: The analytical sample had a mean age of 64.1 years at baseline (SD=2.9) and 53% were women. Incident dementia was detected in 1762 participants (median follow-up time=8.0 years). High frailty was associated with increased dementia risk independently of genetic risk (HR 3.68, 95% CI 3.11 to 4.35). Frailty mediated 44% of the relationship between healthy lifestyle behaviours and dementia risk (indirect effect HR 0.95, 95% CI 0.95 to 0.96). Participants at high genetic risk and with high frailty had 5.8 times greater risk of incident dementia compared with those at low genetic risk and with low frailty (HR 5.81, 95% CI 4.01 to 8.42). Higher genetic risk was most influential in those with low frailty (HR 1.31, 95% CI 1.22 to 1.40) but not influential in those with high frailty (HR 1.09, 95% CI 0.92 to 1.28).Conclusion: Frailty is strongly associated with dementia risk and affects the risk attributable to genetic factors. Frailty should be considered an important modifiable risk factor for dementia and a target for dementia prevention strategies, even among people at high genetic risk. [ABSTRACT FROM AUTHOR]

Main Problem: Frailty is an established risk factor for cognitive decline and Alzheimer's disease. Few studies have examined the longitudinal relationship between frailty and cognition. Methods: Participants of Rush Memory and Aging project (n = 625, 67.5% female, 83.2 ± 5.9 years at baseline) underwent annual clinical evaluations (average follow‐up 5.6 ± 3.7 years) followed by neuropathologic assessment after death. A frailty index was calculated from 41 health variables at each evaluation. Clinical diagnosis of MCI and/or dementia was ascertained by clinical data review (blinded to neuropathological data) after death. Age, sex, education, and neuropathological burden (10‐item index) were evaluated as covariates. Frailty trajectories were calculated using a mixed effects model. Results: At baseline the mean frailty index = 0.24 ± 0.12 and increased at rate of 0.026 or ~1 deficit per year. At death, 27.7% of the sample had MCI, and 38.6% had dementia. Frailty trajectories were significantly steeper among those individuals who were ultimately diagnosed as clinically impaired prior to death, even after controlling for age, sex, education, and neuropathological index. Conclusions: Findings suggest a strong link between health status (frailty index) and dementia, even after considering neuropathology. Frailty trajectories were associated with risk for MCI and dementia, underscoring the importance of addressing frailty to manage dementia risk. [ABSTRACT FROM AUTHOR]

Risk factors for developing dementia from mild cognitive impairment (MCI) probably differ between MCI subtypes. We investigated how frailty relates to dementia risk in amnestic MCI (a-MCI; n = 2,799) and non-amnestic MCI (na-MCI; n = 629) in the National Alzheimer's Coordinating Center database. Although higher frailty increased dementia risk for people with either a-MCI or na-MCI, the larger risk was in na-MCI (interaction hazard ratio = 1.35 [95% confidence interval = 1.15-1.59], p < 0.001). Even after the onset of clinically significant cognitive impairment, poor general health, quantified by a high degree of frailty, is a significant risk for dementia. ANN NEUROL 2021;89:1221-1225. [ABSTRACT FROM AUTHOR]

Objective: To determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype.Methods: A frailty index was calculated using the deficit-accumulation approach in participants aged 50 years and older from the National Alzheimer's Coordinating Center. Cognitive status was determined by clinical evaluation. Using multistate transition models, we assessed the extent to which an increasing degree of frailty affected the probabilities of transitioning between not cognitively impaired (NCI), MCI, and dementia.Results: Participants (n=14 490) had a mean age of 72.2 years (SD=8.9 years; range=50-103 years). Among those NCI at baseline (n=9773), each 0.1 increment increase in the frailty index was associated with a higher risk of developing MCI and a higher risk of progressing to dementia. Among those with MCI at baseline (n=4717), higher frailty was associated with a higher risk of progressing to dementia, a lower probability of being reclassified as NCI, and a higher likelihood of returning to MCI in those that were reclassified as NCI. These risk effects were present and similar in both carriers and non-carriers of the APOE ε4 allele.Conclusion: Among older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value. [ABSTRACT FROM AUTHOR]

Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly. Thus, we examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age = 72.2) were recruited from the Czech Brain Aging Study and, based on APOE and BDNF genes polymorphisms, were divided into four groups: ɛ4-BDNFVal/Val (n = 37), ɛ4-BDNFMet (n = 19), ɛ4+BDNFVal/Val (n = 35), and ɛ4+BDNFMet (n = 16). All patients underwent clinical examination, magnetic resonance imaging, and complex neuropsychological battery. The combination of APOEɛ4+ and BDNF Met was associated with significantly worse memory performance in immediate and delayed recall compared to other polymorphism groups. We did not observe increased atrophy in areas related to memory function in the ɛ4+BDNFMet group. Our findings suggest that carriage of ɛ4+BDNFMet is associated with more pronounced memory dysfunction, a typical feature of early AD, but not with structural brain changes in aMCI patients. These findings suggest that in APOEɛ4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes. [ABSTRACT FROM AUTHOR]

Previous longitudinal evidence has demonstrated frailty and depression to be closely related (Collard I et al. i , 2015; Soysal I et al. i , 2017). What this investigation does contribute clearly, however, is further evidence of the dramatic increase in the risk of death due to advancing frailty, with this risk probably increasing further, in many individuals, if depressive symptoms are also present. This may also be related to how frailty is conceptualized given that depressive symptoms are integral to the frailty phenotype, but can be studied independently with the deficit-accumulation model. [Extracted from the article]

Cognitive reserve (CR) is a theoretical construct describing the underlying cognitive capacity of an individual that confers differential levels of resistance to, and recovery from, brain injuries of various types. To date, estimates of an individual's level of CR have been based on single proxy measures that are retrospective and static in nature. To develop a measure of dynamic change in CR across a lifetime, we previously identified a latent factor, derived from an exploratory factor analysis of a large sample of healthy older adults, as current CR (cCR). In the present study, we examined the longitudinal results of a sample of 272 older adults enrolled in the Tasmanian Healthy Brain Project. Using results from 12-month and 24-month reassessments, we examined the longitudinal validity of the cCR factor using confirmatory factor analyses. The results of these analyses indicate that the cCR factor structure is longitudinally stable. These results, in conjunction with recent results from our group demonstrating dynamic increases in cCR over time in older adults undertaking further education, lend weight to this cCR measure being a valid estimate of dynamic change in CR over time. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) offers significant insight into the complex organization of neural networks within the human brain. Using resting-state functional MRI data, topological maps can be created to visualize changes in brain activity, as well as to represent and assess the structural and functional connections between different brain regions. Crucially, Alzheimer's disease (AD) is associated with progressive loss in this connectivity, which is particularly evident within the default mode network. In this paper, we review the recent literature on how factors that are associated with risk of dementia may influence the organization of the brain network structures. In particular, we focus on cognitive reserve and the common genetic polymorphisms of APOE and BDNF Val66Met. [ABSTRACT FROM AUTHOR]

The transfer impedances of current transducers are estimated using a special calibration fixture, which is often assumed to be perfectly matched at its coaxial ports. However, the errors inherent in this approximation increase with frequency, making the measurement of cable currents increasingly inaccurate at higher frequencies. A one-dimensional (1-D) transmission line model is proposed to account for such errors in a calibration fixture of simple design by using additional measurements to quantify the mismatches in the system. This technique is validated using a numerical model of such a calibration fixture as well against experimental data and numerical predictions for the current induced on a wire inside a rectangular cavity due to an external source that is coupled into the interior via an aperture. It is concluded that the proposed approach provides improved results with a calibration fixture of simple design for frequencies up to at least 600 MHz. Index Terms--Calibration, current measurement, electronic analysis, electromagnetic compatibility (EMC), electromagnetic measurements, scattering parameters, transmission line matrix methods, transmission line theory.

Background:Cognitive reserve (CR) is a protective factor that supports cognition by increasing the resilience of an individual's cognitive function to the deleterious effects of cerebral lesions. A single environmental proxy indicator is often used to estimate CR (e.g. education), possibly resulting in a loss of the accuracy and predictive power of the investigation. Furthermore, while estimates of an individual's prior CR can be made, no operational measure exists to estimate dynamic change in CR resulting from exposure to new life experiences.Methods:We aimed to develop two latent measures of CR through factor analysis: prior and current, in a sample of 467 healthy older adults.Results:The prior CR measure combined proxy measures traditionally associated with CR, while the current CR measure combined variables that had the potential to reflect dynamic change in CR due to new life experiences. Our main finding was that the analyses uncovered latent variables in hypothesized prior and current models of CR.Conclusions:The prior CR model supports multivariate estimation of pre-existing CR and may be applied to more accurately estimate CR in the absence of neuropathological data. The current CR model may be applied to evaluate and explore the potential benefits of CR-based interventions prior to dementia onset. [ABSTRACT FROM PUBLISHER]

This paper presents a detailed analysis of the behavior of a novel fault-tolerant 32-bit embedded CPU as compared to a default (non-fault-tolerant) implementation of the same processor during a fault injection campaign of single and double faults. The fault-tolerant processor tested is characterized by per-cycle voting of microarchitectural and the flop-based architectural states, redundancy at the pipeline level, and a distributed voting scheme. Its fault-tolerant behavior is characterized for three different workloads from the automotive application domain. The study proposes statistical methods for both the single and dual fault injection campaigns and demonstrates the fault-tolerant capability of both processors in terms of fault latencies, the probability of fault manifestation, and the behavior of latent faults. [ABSTRACT FROM AUTHOR]

Focuses on electromagnetic compatibility (EMC) of the electronic component of vehicles. Concept of intelligent transport system; Validation of automotive products for EMC compliance.

Background: Within the National Alzheimer's Coordinating Center (NACC) dataset, we quantified the associations of frailty and global neuropathological burden with clinical dementia severity, and explored whether frailty influences the expression of dementia at a given level of neuropathology. Method: The sample included 2,621 individuals who had available clinical data and had undergone autopsy within 24 months of their last study visit. A 32‐item frailty index (FI) was calculated retrospectively using the deficit accumulation approach, and a measure of global neuropathological burden (NP) was calculated using a similar index approach from 12 markers of brain disease (e.g. neurofibrillary tangle Braak stage, density of neocortical neuritic plaques, severity of cerebral amyloid angiopathy, presence of microinfarcts). Linear models were used to model the change in the 18‐point Clinical Dementia Rating Scale sum of boxes score (CDR‐SB) per 10% increase in either the FI score or NP score, after adjusting for age, sex, education level, primary language, time from clinical assessment to autopsy, and APOE ε4 allelic status. Result: The analytical sample was 80.8 years old (SD = 9.4 years, range = 60 – 100 years), on average. Each 10% increase in either measure was associated with a significantly higher CDR‐SB (FI: 2.41 points [95% CI = 2.27, 2.56]; NP: 0.87 points [95% CI = 0.73, 1.01]). A significant interaction indicated that the relationship between NP and CDR‐SB became weaker for each 10% increase in FI (P =.001). The largest increase in CDR‐SB due to a 10% increase in NP was observed among the least frail individuals (FI < 0.3; 1.15 points [95% CI = 0.91, 1.39]), with smaller and similar increases in CDR‐SB observed in both medium (FI ≥ 0.3; 0.77 points [95% CI = 0.47, 1.07]) and high frailty (FI ≥ 0.5, 0.73 points [95% CI = 0.39, 1.07]) groups. Conclusion: An increasing degree of frailty and neuropathology are each independently associated with more severe impairment. Among the least frail individuals, neuropathological burden is closely related to clinical function, whereas clinical impairment may occur even at a low level of neuropathology in those who are more frail. [ABSTRACT FROM AUTHOR]

Brain-derived neurotropic factor (BDNF) is an abundant and multi-function neurotrophin in the brain. It is released following neuronal activity and is believed to be particularly important in strengthening neural networks. A common variation in the BDNF gene, a valine to methionine substitution at codon 66 (Val66Met), has been linked to differential expression of BDNF associated with experience-dependent plasticity. The Met allele has been associated with reduced production of BDNF following neuronal stimulation, which suggests a potential role of this variation with respect to how the nervous system may respond to challenges, such as brain ageing and related neurodegenerative conditions (e.g., dementia and Alzheimer's disease). The current review examines the potential of the BDNF Val66Met variation to modulate an individual's susceptibility and trajectory through cognitive changes associated with ageing and dementia. On balance, research to date indicates that the BDNF Met allele at this codon is potentially associated with a detrimental influence on the level of cognitive functioning in older adults and may also impart increased risk of progression to dementia. Furthermore, recent studies also show that this genetic variation may modulate an individual's response to interventions targeted at building cognitive resilience to conditions that cause dementia. [ABSTRACT FROM AUTHOR]

Assessing physiological changes that occur with healthy ageing is prerequisite for understanding pathophysiological age-related changes. Eye movements are studied as biomarkers for pathological changes because they are altered in patients with neurodegenerative disorders. However, there is a lack of data from large samples assessing age-related physiological changes and sex differences in oculomotor performance. Thus, we assessed and quantified cross-sectional relations of age and sex with oculomotor performance in the general population. We report results from the first 4,000 participants (aged 30-95 years) of the Rhineland Study, a community-based prospective cohort study in Bonn, Germany. Participants completed fixation, smooth pursuit, prosaccade and antisaccade tasks. We quantified associations of age and sex with oculomotor outcomes using multivariable linear regression models. Performance in 12 out of 18 oculomotor measures declined with increasing age. No differences between age groups were observed in five antisaccade outcomes (amplitude-adjusted and unadjusted peak velocity, amplitude gain, spatial error and percentage of corrected errors) and for blink rate during fixation. Small sex differences occurred in smooth pursuit velocity gain (men have higher gain) and blink rate during fixation (men blink less). We conclude that performance declines with age in two thirds of oculomotor outcomes but that there was no evidence of sex differences in eye movement performance except for two outcomes. Since the percentage of corrected antisaccade errors was not associated with age but is known to be affected by pathological cognitive decline, it represents a promising candidate preclinical biomarker of neurodegeneration. [ABSTRACT FROM AUTHOR]