Bridging Patterns of Neurocognitive Aging Across the Older Adult Lifespan

Magnetic resonance imaging (MRI) studies of brain and neurocognitive aging rarely include oldest-old adults (ages 85+). But predictions of neurocognitive aging theories derived from MRI findings in younger-old adults (ages 65-85) may not generalize into advanced age, particularly given the increased prevalence of cognitive impairment/dementia in the oldest-old. Here, we reviewed the MRI literature in oldest-old adults and interpreted findings within the context of regional variation, compensation, brain maintenance, and reserve theories. Structural MRI studies revealed regional variation in brain aging as larger age effects on medial temporal and posterior regions for oldest-old than younger-old adults. They also revealed that brain maintenance explained preserved cognitive functioning into the tenth decade of life. Very few functional MRI studies support compensatory activity in oldest-old adults who perform as well as younger groups, although there was evidence that higher brain reserve in oldest-old adults may mediate effects of brain aging on cognition. Despite some continuity, different cognitive and neural profiles across the older adult lifespan should be addressed in modern neurocognitive aging theories.

Association Between Peripheral Blood Levels of Vitamin A and Autism Spectrum Disorder in Children: A Meta-Analysis

Vitamin A is an essential fat-soluble micronutrient that plays important roles in a surprisingly wide variety of biological processes from early growth and development to brain maintenance. Numerous clinical studies have been conducted to explore the relationship between peripheral vitamin A levels and autism spectrum disorder (ASD), but the results of these studies are controversial. Therefore, we assessed the association between peripheral vitamin A levels and ASD in the present meta-analysis. Relevant records were retrieved through the Embase, Web of Knowledge and PubMed databases up to 13 November 2020. Reference lists were also searched and analyzed. Hedges' g with its corresponding 95% confidence interval (CI) was used to assess the association between peripheral vitamin A levels and ASD. A fixed or random effects model was selected according to a heterogeneity test in overall and subgroup analyses. Five records (six studies) with 935 ASD children and 516 healthy children were included in the present study. Significantly decreased peripheral vitamin A concentrations were observed in ASD children compared with healthy children (Hedges' g = −0.600, 95% CI −1.153 to −0.048, P = 0.033). A similar result was also obtained after removing the studies identified by Galbraith plots. In addition, no obvious publication bias was found in the meta-analysis. The findings of our meta-analysis suggested decreased peripheral vitamin A levels in ASD children compared with healthy children. Further investigations into the effects of vitamin A on the development of ASD are warranted.

Examining the Role of the Noradrenergic Locus Coeruleus for 2 Predicting Attention and Brain Maintenance in Healthy Old Age 3 and Disease: An MRI Structural Study for the Alzheimer’s Disease 4 Neuroimaging Initiative

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Examining the Role of the Noradrenergic Locus Coeruleus for 2 Predicting Attention and Brain Maintenance in Healthy Old Age 3 and Disease: An MRI Structural Study for the Alzheimer’s Disease 4 Neuroimaging Initiative

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Examining the Role of the Noradrenergic Locus Coeruleus for Predicting Attention and Brain Maintenance in Healthy Old Age, Mild Cognitive Impairment and Alzheimer’s Disease: An MRI Structural Study On the Adni Cohort

The Noradrenergic Theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the up-regulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test this theory, a study was conducted on a sample of 686 participants (395 Controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC vol-ume, attentional performance and a biological index of brain maintenance (BrainPAD – a measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on reserve indices including education and occupational attainment. Volumetric variation across groups was also explored. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic hypothesis. Results showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on upregulation of the noradrenergic system (e.g. attention training, physical exercise and pharmacological intervention) may yield important clin-ical benefits to mitigate cognitive impairment with age and disease.

IQ moderation of cognitive decline supports cognitive reserve and not brain maintenance

BackgroundWhile cognitive decline has been frequently reported in aging research, moderating factors for cognitive changes in healthy aging have been inconclusive. This study evaluated 5-year changes in four cognitive abilities and the potential moderation of age and cognitive reserve (CR) factors on cognitive changes.MethodsParticipants included 254 healthy adults initially aged 20 – 80 years. Six tasks estimated each of the four abilities: fluid reasoning, processing speed, memory and vocabulary. The proxies for CR included years of education and IQ. Cognitive changes and moderating factors were examine using multiple indicator latent change score model. Change point analysis pinpointed inflection points after which cognitive changes accelerated.ResultsThere was significant decline over five years in fluid reasoning, processing speed and memory, with age moderation such that older age was associated with steeper decline. Accelerated decline was observed earlier for reasoning and speed, at ages 58 and 59 years respectively, than for memory, at age 70 years. Vocabulary continued to improve until reaching peak performance at 67 years. For moderation of cognitive changes by CR proxies, while education did not show significant moderation, higher IQ was associated with reduced 5-year decline in reasoning and memory but not processing speed. CR moderation effect was found to be independent of mean cortical thickness.ConclusionsUsing a robust statistical model to estimate the latent change in four cognitive abilities over 5 years, the results showed that cognitive reserve rather than brain maintenance is the potential mechanism underlying IQ’s protective effect on cognitive decline.HighlightsReasoning and processing speed show accelerated decline after ages 59 and 58 years, respectively.Memory shows accelerated decline after age 70 years.Vocabulary performance peaks at age 67 years.Higher IQ is protective of cognitive decline in reasoning and memory but not for processing speed.IQ’s protective effect on cognition is independent of brain maintenance.

Innovative Experiences at Work Support Hippocampal Maintenance in Late Life

Prior research has demonstrated the positive impact of occupational complexity on cognitive aging, however, neural underpinnings remain unclear. There is emerging evidence linking midlife managerial experience to slower hippocampal atrophy (Suo et al., 2012, 2017), supporting the brain maintenance model (i.e. preservation of young-like brain structure). However, occupational complexity, along with education, is known to be a proxy of cognitive reserve (i.e. mind’s resistance to brain aging). The current study examined the influence of midlife work environment factors (i.e., autonomy, control, and innovation; Work Environment Scale, Moos, 1981) on change in hippocampal thickness, while controlling for education and age. We studied 150 participants (60-78 years, M = 66.27, SD = 5.20, 61% female) from the Seattle Longitudinal Study who had at least one MRI scan and remained cognitively normal between 2006 and 2014. Hypotheses were tested using multilevel modeling in Mplus; gender differences were examined. There was no substantial drop in model fit as a result of adding any of the significant effects. Innovation at work slowed the decrease in hippocampal thickness over time demonstrating the protective effect of more novelty, variety and change in work activities. There was a significant age by gender interaction, such that the decrease in hippocampal thickness was stronger for older women. Together, findings suggest that long-term impact of work environment on the hippocampus extends beyond the effects of education, particularly in men, supporting the brain maintenance hypothesis. Innovation at work should be considered in understanding protective/risk factors in hippocampal atrophy in older age.