Fetal influence on the human brain through the lifespan.

Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4-82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

Cognitive and hippocampal changes weeks and years after memory training.

While immediate effects of memory-training are widely reported in young and older adults, less is known regarding training-dependent hippocampal plasticity across multiple intervention phases, and long-term maintenance of such. Here, 157 healthy young and older adults underwent a training-intervention including two 10 weeks periods of episodic-memory training, separated by two 2 weeks periods of no training. Both age groups showed improvements on a criterion task, which prevailed after 3 years. When compared to the reference condition of no training, relative increases in hippocampal volume were observed after the training across age groups, which were maintained after 10 weeks periods of no training. However, there was age-group dependent temporal variation with respect to timing of effects. Hippocampal volume of the training group did not differ from that of a passive control-group 3 years after the intervention. The young showed an immediate near-transfer effect on a word-association task. We show that training-gains on memory performance can prevail for at least 3 years. Memory training can induce increases in hippocampal volume immediately after the intervention and after months. Episodic-memory training can produce transfer effects to a non-trained memory task in young adults. However, maintained effects on hippocampal volume beyond 10 weeks are uncertain, and likely require continuous training.

Risk- and protective factors for memory plasticity in aging.

Risk and protective factors for cognitive function in aging may affect how much individuals benefit from their environment or life experiences by preserving or improving cognitive abilities. We investigated the relations between such factors and outcome from episodic-memory training in 136 healthy young and older adults. Tested risk factors included carrying the ɛ4 variant of the apolipoprotein E allele (APOE), age, body mass index, blood pressure, and cholesterol. Protective factors included higher levels of education, intelligence quotient (IQ), physical activity, fatty acids, and vitamin D. Average increases in memory performance were seen after training, with ample variation between individuals. Being young, female, and having higher IQ were positive predictors of memory improvement. No other relationships were observed. Similar benefit was observed across APOE allelic variation. This indicates that beyond IQ, age, and sex, known risk -and protective factors of cognitive function in aging were not significantly related to memory plasticity.

Within-session verbal learning slope is predictive of lifespan delayed recall, hippocampal volume, and memory training benefit, and is heritable.

Memory performance results from plasticity, the ability to change with experience. We show that benefit from practice over a few trials, learning slope, is predictive of long-term recall and hippocampal volume across a broad age range and a long period of time, relates to memory training benefit, and is heritable. First, in a healthy lifespan sample (n = 1825, age 4-93 years), comprising 3483 occasions of combined magnetic resonance imaging (MRI) scans and memory tests over a period of up to 11 years, learning slope across 5 trials was uniquely related to performance on a delayed free recall test, as well as hippocampal volume, independent from first trial memory or total memory performance across the five learning trials. Second, learning slope was predictive of benefit from memory training across ten weeks in an experimental subsample of adults (n = 155). Finally, in an independent sample of male twins (n = 1240, age 51-50 years), learning slope showed significant heritability. Within-session learning slope may be a useful marker beyond performance per se, being heritable and having unique predictive value for long-term memory function, hippocampal volume and training benefit across the human lifespan.

Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression.

Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker ß-amyloid (Aß). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aß accumulation. Here, we tested whether the relationship between cortical Aß accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aß correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aß relationship followed closely the Aß accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aß accumulation may involve Homer1 activity in the cortical regions, where harbor Aß deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

Multimodal cortical and hippocampal prediction of episodic-memory plasticity in young and older adults.

Episodic memory can be trained in both early and late adulthood, but there is considerable variation in cognitive improvement across individuals. Which brain characteristics make some individuals benefit more than others? We used a multimodal approach to investigate whether volumetric magnetic resonance imaging (MRI) and resting-state functional MRI characteristics of the cortex and hippocampus, brain regions involved in episodic-memory function, were predictive of cognitive improvement after memory training. We hypothesized that these brain characteristics would differentially predict memory improvement in young and older adults, given the vulnerability of cortical regions as well as the hippocampus to healthy aging. Following structural and resting-state activity magnetic resonance scans, 50 young and 76 older participants completed 10 weeks of strategic episodic-memory training. Both age groups improved their memory performance, but the young adults more so than the older. Vertex-wise analyses of cortical volume showed no significant relation to memory benefit. When analyzing the two age groups separately, hippocampal volume was predictive of memory improvement in the group of older participants only. In this age group, the lower resting-state activity of the hippocampus was also predictive of memory improvement. Both volumetric and resting-state characteristics of the hippocampus explained unique variance of the improvement in the older participants suggesting that a multimodal imaging approach is valuable for the understanding of mechanisms underlying memory plasticity in aging.

The Temporal Dynamics of Brain Plasticity in Aging.

Cognitive training has been suggested as a possible remediation of decline in brain structure with older age. However, it is unknown whether training effects are transient or enduring, as no studies have examined training-induced plasticity relative to decline in older adults across extended periods with multiple intervention phases. We investigated the temporal dynamics of brain plasticity across periods on and off memory training, hypothesizing that (1) a decline in white matter (WM) microstructure would be observed across the duration of the study and (2) that periods of memory training would moderate the WM microstructural decline. In total, 107 older adults followed a 40-week program, including 2 training periods separated by periods with no intervention. The general decline in WM microstructure observed across the duration of the study was moderated following the training periods, demonstrating that cognitive training may mitigate age-related brain deterioration. The training-related improvements were estimated to subside over time, indicating that continuous training may be a premise for the enduring attenuation of neural decline. Memory improvements were largely maintained after the initial training period, and may thus not rely on continuous training to the same degree as WM microstructure.

The effects of memory training on behavioral and microstructural plasticity in young and older adults.

Age differences in human brain plasticity are assumed, but have not been systematically investigated. In this longitudinal study, we investigated changes in white matter (WM) microstructure in response to memory training relative to passive and active control conditions in 183 young and older adults. We hypothesized that (i) only the training group would show improved memory performance and microstructural alterations, (ii) the young adults would show larger memory improvement and a higher degree of microstructural alterations as compared to the older adults, and (iii) changes in memory performance would relate to microstructural alterations. The results showed that memory improvement was specific to the training group, and that both the young and older participants improved their performance. The young group improved their memory to a larger extent compared to the older group. In the older sample, the training group showed less age-related decline in WM microstructure compared to the control groups, in areas overlapping the corpus callosum, the cortico-spinal tract, the cingulum bundle, the superior longitudinal fasciculus, and the anterior thalamic radiation. Less microstructural decline was related to a higher degree of memory improvement. Despite individual adaptation securing sufficient task difficulty, no training-related group differences in microstructure were found in the young adults. The observed divergence of behavioral and microstructural responses to memory training with age is discussed within a supply-demand framework. The results demonstrate that plasticity is preserved into older age, and that microstructural alterations may be part of a neurobiological substrate for behavioral improvements in older adults. Hum Brain Mapp 38:5666-5680, 2017. © 2017 Wiley Periodicals, Inc.

White matter integrity as a marker for cognitive plasticity in aging.

Age-related differences in white matter (WM) integrity are substantial, but it is unknown whether between-subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging.

Premises of plasticity - And the loneliness of the medial temporal lobe.

In this perspective paper, we examine possible premises of plasticity in the neural substrates underlying cognitive change. We take the special role of the medial temporal lobe as an anchoring point, but also investigate characteristics throughout the cortex. Specifically, we examine the dimensions of evolutionary expansion, heritability, variability of morphometric change, and inter-individual variance in myelination with respect to the plastic potential of different brain regions. We argue that areas showing less evolutionary expansion, lower heritability, greater variability of cortical thickness change through the lifespan, and greater inter-individual differences in intracortical myelin content have a great extent of plasticity. While different regions of the brain show these features to varying extent, analyses converge on the medial temporal lobe including the hippocampi as the target of all these premises. We discuss implications for effects of training on brain structures, and conditions under which plasticity may be evoked.

[An outbreak of MRSA in a nursing home in Oslo]. / Et MRSA-utbrudd i et sykehjem i Oslo.

BACKGROUND: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) represent an increasing problem in Norway, also in nursing homes and other institutions for long-term care. We describe an outbreak of MRSA in a nursing home in Oslo 2004-5. MATERIAL AND METHODS: The nursing home has six wards with 185 beds. The building is old, all rooms have toilets and sinks, but showers are shared. Standard screening procedures were carried out according to the national MRSA guide and by using the nursing home's infection control programme. Later on we used more extensive screening of staff and patients. RESULTS: The outbreak started in a ward for short-term care, but spread to a ward for patients with dementia after some months. Ten patients, seven staff members and two relatives of infected persons were diagnosed with MRSA. All bacteria probably belonged to the same strain. Four staff members and five patients who were infected had pre-existing wounds or eczema. The nursing home was declared free of MRSA 20 months after the outbreak started, but one member of staff remained a carrier for two years, and one patient became a chronic carrier of MRSA. During the first six months, infected patients were restricted to their rooms, and standard eradication procedures were carried out for five days. Later on, we introduced cohort isolation for infected, exposed and recently treated patients, a different screening routine, a prolonged eradication procedure, restrictions on staff working elsewhere and more stringent precautions for visitors. INTERPRETATION: An old building and insufficient isolation procedures during the first phase of the outbreak contributed to spreading MRSA and prolonging the outbreak. Cohort isolation seemed to be the most important measure to control the outbreak. All nursing homes should have a designated single patient room for contact precautions. Long-term carriers of MRSA in nursing homes represent a big challenge.