Several concepts, which in the aggregate get might be used to account for “resilience” against age- and disease-related changes, have been the subject of much research. These include brain reserve, ...cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.
Background
No studies have examined the longitudinal association between the persistence of pain and its relationship to cognitive problems in older adults. The objective of this study was to examine ...how the persistent of pain associates with cognitive performance, cognitive impairment, and subjective memory decline.
Methods
Across 10 biennial waves, 8515 adults ages 65 and over were assessed from the Health and Retirement Study (Mage = 74.17, SD = 6.87, 59.2% female). At each wave, individuals were asked to report on pain presence, and if present, rate its intensity and interference with daily activities such as housework or chores. Using running frequencies or averages, we calculated the persistence of pain using these three pain measures. Cognition was assessed using cognitive performance and different cognitive impairment cutoffs. Incident subjective memory decline was additionally measured as new self‐reported memory change in the last 2 years. General estimating equations examined concurrent associations between persistence of pain and cognitive variables, adjusting for demographics, depressive symptoms, and medical comorbidities.
Results
Persistence of pain presence was associated with an increased risk of cognitive impairment. Only persistence of pain interference, not pain intensity, was significantly associated with poorer cognitive performance or being classified as cognitively impaired. For every 2 years, persistence of pain interference was associated with 21% increased odds of cognitive impairment. Only one of three pain variables was related to incident subjective memory decline.
Conclusions
Persistence of pain is associated with poorer cognitive performance in community‐dwelling older adults, especially when involving ongoing interference in chores and work. Facilitating pain management might be important for helping to maintain later‐life cognition and reduce dementia risk.
We tested if cognitive and brain reserve and maintenance explain individual differences in episodic memory and other cognitive domains from late middle to early older adulthood. We used The Vietnam ...Era Twin Study of Aging data (n=1604 men) with episodic memory measured at mean ages of 56, 62 and 68 years, and magnetic resonance imaging data for a subsample of participants (n=321). Cognitive reserve —young adult general cognitive ability at a mean age of 20 years and, to a lesser degree, educational attainment— was positively related to episodic memory performance at each assessment, but not to memory change. We found no evidence for the associations of brain reserve or brain maintenance on memory change. Results were highly similar when looking at processing speed, executive function and verbal fluency. In conclusion, higher young adult cognitive reserve was related to better episodic memory in midlife and older adulthood, but it did not confer better cognitive maintenance with respect to memory. This supports the importance of early cognitive development in dementia prevention.
•On average episodic memory declines in late midlife.•Young adult general cognitive ability predicts episodic memory in aging.•General cognitive ability does not modify the rate of episodic memory change.•Results are similar for executive function, processing speed and verbal fluency.
Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a ...product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51–59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
VETSA: the Vietnam Era Twin Study of Aging Kremen, William S; Franz, Carol E; Lyons, Michael J
Twin research and human genetics,
02/2013, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men. It comprises a subset of over 1,200 twins from the ...Vietnam Era Twin Registry. Like many other studies of aging, the VETSA includes many different phenotypes, but there are some key features that distinguish it from most other behavioral genetic aging studies. First, the initial assessment was conducted when all participants were middle-aged. Second, the age range of participants is narrow; all were in their 50s at the time of the initial recruitment. Third, the study includes an extensive and demanding neurocognitive test battery that was designed to provide good coverage of different cognitive abilities and avoid ceiling effects in middle-aged adults. Fourth, young adult cognitive test data (at an average age of 20 years) are available to provide a gauge of cognitive change. These features make the VETSA ideal for studying the heterogeneity of within-individual trajectories from midlife to old age, and for early detection of risk factors for cognitive decline.
How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in ...cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56–66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation—namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.
While genome wide association studies (GWASs) of Alzheimer's Disease (AD) in European (EUR) ancestry cohorts have identified approximately 83 potentially independent AD risk loci, progress in ...non-European populations has lagged. In this study, data from the Million Veteran Program (MVP), a biobank which includes genetic data from more than 650,000 US Veteran participants, was used to examine dementia genetics in an African descent (AFR) cohort. A GWAS of Alzheimer's disease and related dementias (ADRD), an expanded AD phenotype including dementias such as vascular and non-specific dementia that included 4012 cases and 18,435 controls age 60+ in AFR MVP participants was performed. A proxy dementia GWAS based on survey-reported parental AD or dementia (n = 4385 maternal cases, 2256 paternal cases, and 45,970 controls) was also performed. These two GWASs were meta-analyzed, and then subsequently compared and meta-analyzed with the results from a previous AFR AD GWAS from the Alzheimer's Disease Genetics Consortium (ADGC). A meta-analysis of common variants across the MVP ADRD and proxy GWASs yielded GWAS significant associations in the region of APOE (p = 2.48 × 10
), in ROBO1 (rs11919682, p = 1.63 × 10
), and RNA RP11-340A13.2 (rs148433063, p = 8.56 × 10
). The MVP/ADGC meta-analysis yielded additional significant SNPs near known AD risk genes TREM2 (rs73427293, p = 2.95 × 10
), CD2AP (rs7738720, p = 1.14 × 10
), and ABCA7 (rs73505251, p = 3.26 × 10
), although the peak variants observed in these genes differed from those previously reported in EUR and AFR cohorts. Of the genes in or near suggestive or genome-wide significant associated variants, nine (CDA, SH2D5, DCBLD1, EML6, GOPC, ABCA7, ROS1, TMCO4, and TREM2) were differentially expressed in the brains of AD cases and controls. This represents the largest AFR GWAS of AD and dementia, finding non-APOE GWAS-significant common SNPs associated with dementia. Increasing representation of AFR participants is an important priority in genetic studies and may lead to increased insight into AD pathophysiology and reduce health disparities.
Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to ...whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.
Genetic topography of brain morphology Chen, Chi-Hua; Fiecas, Mark; Gutierrez, E. D. ...
Proceedings of the National Academy of Sciences - PNAS,
10/2013, Letnik:
110, Številka:
42
Journal Article
Recenzirano
Odprti dostop
Animal data show that cortical development is initially patterned by genetic gradients largely along three orthogonal axes. We previously reported differences in genetic influences on cortical ...surface area along an anterior-posterior axis using neuroimaging data of adult human twins. Here, we demonstrate differences in genetic influences on cortical thickness along a dorsal-ventral axis in the same cohort. The phenomenon of orthogonal gradations in cortical organization evident in different structural and functional properties may originate from genetic gradients. Another emerging theme of cortical patterning is that patterns of genetic influences recapitulate the spatial topography of the cortex within hemispheres. The genetic patterning of both cortical thickness and surface area corresponds to cortical functional specializations. Intriguingly, in contrast to broad similarities in genetic patterning, two sets of analyses distinguish cortical thickness and surface area genetically. First, genetic contributions to cortical thickness and surface area are largely distinct; there is very little genetic correlation (i.e., shared genetic influences) between them. Second, organizing principles among genetically defined regions differ between thickness and surface area. Examining the structure of the genetic similarity matrix among clusters revealed that, whereas surface area clusters showed great genetic proximity with clusters from the same lobe, thickness clusters appear to have close genetic relatedness with clusters that have similar maturational timing. The discrepancies are in line with evidence that the two traits follow different mechanisms in neurodevelopment. Our findings highlight the complexity of genetic influences on cortical morphology and provide a glimpse into emerging principles of genetic organization of the cortex.
PDF
