General session: III. Heredity counseling

ABSTRACT

Aging is a major risk factor for both normal and pathological cognitive decline. However, individuals vary in their rate of age-related decline. We developed an easily interpretable composite measure of cognitive age, and related both the level of cognitive age and cognitive slope to sociodemographic, genetic, and disease indicators and examined its prediction of dementia transition. Using a sample of 19,594 participants from the Health and Retirement Study, cognitive age was derived from a set of performance tests administered at each wave. Our findings reveal different conclusions as they relate to levels versus slopes of cognitive age, with more pronounced differences by sex and race/ethnicity for absolute levels of cognitive decline rather than for rates of declines. We also find that both level and slope of cognitive age are inversely related to education, as well as increased for persons with APOE ?4 and/or diabetes. Finally, results show that the slope in cognitive age predicts subsequent dementia among non-demented older adults. Overall, our study suggests that this measure is applicable to cross-sectional and longitudinal studies on cognitive aging, decline, and dementia with the goal of better understanding individual differences in cognitive decline.     

Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936

As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms ( SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimer's disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN . Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 ( P   <   0.05). No SNPs reached the Bonferroni-level of significance (all P   >   0.0015). Of the 10 genes, we discuss that COMT , KL , PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition.     

Early cognitive experience prevents adult deficits in a neurodevelopmental schizophrenia model

Brain abnormalities acquired early in life may cause schizophrenia, characterized by adulthood onset of psychosis, affective flattening, and cognitive impairments. Cognitive symptoms, like impaired cognitive control, are now recognized to be important treatment targets but cognition-promoting treatments are ineffective. We hypothesized that cognitive training during the adolescent period of neuroplastic development can tune compromised neural circuits to develop in the service of adult cognition and attenuate schizophrenia-related cognitive impairments that manifest in adulthood. We report, using neonatal ventral hippocampus lesion rats (NVHL), an established neurodevelopmental model of schizophrenia, that adolescent cognitive training prevented the adult cognitive control impairment in NVHL rats. The early intervention also normalized brain function, enhancing cognition-associated synchrony of neural oscillations between the hippocampi, a measure of brain function that indexed cognitive ability. Adolescence appears to be a critical window during which prophylactic cognitive therapy may benefit people at risk of schizophrenia.     

Psychosocial Working Conditions and Cognitive Complaints among Swedish Employees

Background

Cognitive complaints involving problems with concentration, memory, decision-making and thinking are relatively common in the work force. The sensitivity of both subjective and objective cognitive functioning to common psychiatric conditions, stress levels and to cognitive load makes it plausible that psychosocial working conditions play a role in cognitive complaints. Thus, this study aimed to test the associations between psychosocial work factors and cognitive complaints in nationally representative samples of the Swedish work force. Cross-sectional (n = 9751) and prospective (n = 3644; two time points two years apart) sequential multiple regression analyses were run, adjusting for general confounders, depressive- and sleeping problems. Additional prospective analyses were run adjusting for baseline cognitive complaints.

Cross-sectional results

High quantitative demands, information and communication technology (ICT) demands, underqualification and conflicts were positively associated with cognitive complaints, while social support, good resources at work and overqualification were negatively associated with cognitive complaints in all models. Skill discretion and decision authority were weakly associated with cognitive complaints. Conflicts were more strongly associated with cognitive complaints in women than in men, after adjustment for general confounders.

Prospective results

Quantitative job demands, ICT demands and underqualification were positively associated with future cognitive complaints in all models, including when adjusted for baseline cognitive complaints. Decision authority was weakly positively associated with future cognitive complaints, only after adjustment for depressive- and sleeping problems respectively. Social support was negatively associated with future cognitive complaints after adjustment for general confounders and baseline cognitive complaints. Skill discretion and resources were negatively associated with future cognitive complaints after adjustment for general confounders. The associations between quantitative demands and future cognitive complaints were stronger in women.

Discussion/Conclusions

The findings indicate that psychosocial working conditions should be taken into account when considering cognitive complaints among employees.     

Novel Television-Based Cognitive Training Improves Working Memory and Executive Function

The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60–87 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants'' reports of “adequate” to “high” system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition.     

Longitudinal Associations between Physical and Cognitive Performance among Community-Dwelling Older Adults

To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.     

Nicotine self-medication of cognitive-attentional processing

This article selectively reviews research concerning nicotine's effects on cognition, including the neurobiological mechanism for these effects, task and experimental features that may be important for elucidating these effects, and why these effects may have amplified motivational significance among smokers with cognitive deficit. Nicotine has effects on various cognitive processes, though most studies in humans have focused on the amelioration of cognitive deficits experienced during drug withdrawal. The direct cognitive-enhancing effect of nicotine remains a controversial topic. The relationship between attentional and non-attentional cognitive effects of nicotine is discussed in the context of cognitive self-medication. Further research should include theory-driven examination of cognitive effects of nicotine, and develop targeted smoking cessation programs based on an improved understanding of the role of cognitive self-medication in high-risk individuals.     

长期住院老年精神疾病患者营养状况与认知功能的相关性研究

目的:了解长期住院老年精神疾病患者营养状况及与认知功能的相关性,为临床提供指导。方法:对住院3个月及以上的123例老年精神疾病患者采用简易精神状态检查量表(MMSE)评估认知功能,采用简易微型营养评定精简版(MNA-SF)评估营养状况,并采集一般资料、相关营养生化指标,应用Pearson相关分析MNA-SF评分与MMSE评分的相关性。结果:123例患者中,营养不良风险者67例(54.47%),营养不良者37例(30.08%),营养正常者19例(15.44%)。有认知障碍患者的营养不良发生率显著高于无认知障碍患者营养不良发生率(P<0.05),重度认知障碍者营养不良发生率显著高于轻、中度认知障碍者(P<0.05)。与无认知障碍者比较,中度、重度认知障碍者MNA-SF评分显著降低(P<0.05);与轻度、中度认知障碍者比较,重度认知障碍者MNA-SF评分显著降低(P<0.05)。营养不良者MMSE 6个认知领域评分和认知总评分均显著低于营养不良风险/正常者(P<0.05),Pearson相关分析显示:长期住院老年精神疾病患者MNA-SF评分与MMSE评分呈正相关(r=0.486, P=0.023<0.05)。结论:长期住院老年精神疾病患者营养不良发生率高,且与认知功能密切相关。临床部门需加强老年精神疾病患者,特别是有认知损害老人的营养关切。     

认知风格、内外向和情绪对军人认知反应能力的影响

该文主要通过测评研究认知风格、内外向和情绪对军人认知反应能力的影响。结果表明,场独立性者对图形的认知反应能力比场依赖性者强,情绪稳定性高者的认知反应能力好于情绪稳定性低者,外向性格者的认知反应能力总体上要高于内向性格者。     

Active Cognitive Lifestyle Is Associated with Positive Cognitive Health Transitions and Compression of Morbidity from Age Sixty-Five

Background

Three factors commonly used as measures of cognitive lifestyle are education, occupation, and social engagement. This study determined the relative importance of each variable to long term cognitive health in those with and without severe cognitive impairment.

Methods

Data came from 12,470 participants from a multi-centre population-based cohort (Medical Research Council Cognitive Function and Ageing Study). Respondents were aged 65 years and over and were followed-up over 16 years. Cognitive states of no impairment, slight impairment, and moderate/severe impairment were defined, based on scores from the Mini-Mental State Examination. Multi-state modelling was used to investigate links between component cognitive lifestyle variables, cognitive state transitions over time, and death.

Results

Higher educational attainment and a more complex mid-life occupation were associated with a lower risk of moving from a non-impaired to a slightly impaired state (hazard ratios 0.5 and 0.8), but with increased mortality from a severely impaired state (1.3 and 1.1). More socially engaged individuals had a decreased risk of moving from a slightly impaired state to a moderately/severely impaired state (0.7). All three cognitive lifestyle variables were linked to an increased chance of cognitive recovery back to the non-impaired state.

Conclusions

In those without severe cognitive impairment, different aspects of cognitive lifestyle predict positive cognitive transitions over time, and in those with severe cognitive impairment, a reduced life-expectancy. An active cognitive lifestyle is therefore linked to compression of cognitive morbidity in late life.     

Gray and White Matter Changes in Subjective Cognitive Impairment,Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Voxel-Based Analysis Study

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer''s disease. The subjects in this study were 39 Alzheimer''s disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer''s disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer''s disease.     

What Is the Subjective Cost of Cognitive Effort? Load,Trait, and Aging Effects Revealed by Economic Preference

It has long been assumed that people treat cognitive effort as costly, but also that such effort costs may vary greatly across individuals. Individual differences in subjective effort could present a major and pervasive confound in behavioral and neuroscience assessments, by conflating cognitive ability with cognitive motivation. Self-report cognitive effort scales have been developed, but objective measures are lacking. In this study, we use the behavioral economic approach of revealed preferences to quantify subjective effort. Specifically, we adapted a well-established discounting paradigm to measure the extent to which cognitive effort causes participants to discount monetary rewards. The resulting metrics are sensitive to both within-individual factors, including objective load and reward amount, and between-individual factors, including age and trait cognitive engagement. We further validate cognitive effort discounting by benchmarking it against well-established measures of delay discounting. The results highlight the promise and utility of behavioral economic tools for assessing trait and state influences on cognitive motivation.     

Neurodegenerative properties of chronic pain: cognitive decline in patients with chronic pancreatitis

Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients.     

维持性腹膜透析患者认知功能障碍与营养状况的关系研究

摘要 目的：探究维持性腹膜透析患者认知功能障碍与营养状况的关系。方法：前瞻性纳入2019年1月至2020年6月在济宁医学院附属医院就诊的172例维持性腹膜透析患者，收集患者一般资料。采用蒙特利尔认知评估量表（MoCA）评估患者的认知功能，根据MoCA评分分为认知功能正常组及认知功能障碍组。采用微型营养评估量表（MNA）评估患者营养状态，以MNA评分分为营养正常组、潜在营养不良组、营养不良组，比较认知功能正常组及认知功能障碍组营养状况占比情况，分析维持性腹膜透析患者认知功能与营养状况的相关性及影响认知功能的相关因素。结果：与认知功能正常组比较，认知功能障碍组患者透析时间明显延长，MNA总分、MoCA总分明显降低（P<0.05）。与认知功能正常组比较，认知功能障碍组患者营养正常者比例明显降低，营养不良者比例明显升高（P<0.05），潜在营养不良者比例有所升高但差异无统计学意义（P>0.05）。经Pearson相关性检验分析显示，维持性腹膜透析患者MoCA总分与MNA总分呈明显正相关（P<0.05）。经Logistic回归分析显示，透析时间（延长）、营养不良均为维持性腹膜透析患者认知功能障碍的危险因素（P<0.05）。结论：维持性腹膜透析认知功能障碍患者营养不良发生率明显升高，且患者认知功能障碍与营养状况具有明显相关性，加强患者的营养状况有助于降低认知功能障碍的发生风险。     

认知风格、内外向和情绪对军人认知反应能力的影响

该文主要通过测评研究认知风格、内外向和情绪对军人认知反应能力的影响。结果表明,场独立性者对图形的认知反应能力比场依赖性者强。情绪稳定性高者的认知反应能力好于情绪稳定性低者,外向性格者的认知反应能力总体上要高于内向性格者。     

Diet,inflammation and the gut microbiome: Mechanisms for obesity-associated cognitive impairment

Poor diet and obesity are associated with cognitive impairment throughout adulthood, and increased dementia risk in aging. Here we review the current literature interrogating the mechanisms by which diets high in fat, or fat and sugar lead to cognitive impairment, focusing on changes to gut microbiome composition, inflammatory signalling and blood-brain barrier integrity. Preclinical studies indicate weight gain is not necessary for diet-induced cognitive impairment. Rather, gut microbiome composition, and systemic and central inflammatory processes appear to contribute to diet-induced cognitive impairment. While both obese humans and rodents exhibit reduced blood-brain barrier integrity, cognitive impairments precede these changes, suggesting other mechanisms may underly diet-induced cognitive changes. Other potential candidates include hormone, glucoregulatory and cardiovascular changes. Poor diet and obesity act through multiple mechanisms to affect cognitive health and the challenge for future research is to identify key processes that can be reversed to improve cognition and quality of life.     

Inflammation and Cognition in Older Adults: Evidence from Taiwan

Inflammation has been linked to clinical cognitive impairment, including Alzheimer’s disease. Less is known, however, about the relationship between inflammation and normal, age-associated cognitive decline. An understanding of the determinants of all types of cognitive decline is important for improving quality of life in an aging world. This study investigated whether biomarkers of inflammation were associated with cognitive function and decline in older Taiwanese adults. Data were from the Taiwan Longitudinal Study of Aging and the Social Environment and Biomarkers of Aging Study. Inflammation was measured in 2000 and 2006 as C-reactive protein, interleukin-6, soluble e-selectin, soluble intercellular adhesion molecule-1, and white blood cell count. Cognition was assessed by 10 cognitive and memory tasks, measured in 2006, 2007, and 2011. Growth curve models were used to examine the relationship between inflammation and cognitive score over this time period. Higher levels of inflammation were associated with lower baseline cognitive scores, but not with longitudinal change in cognitive score. This study did not support a causal link between inflammation and cognitive decline among this older cohort. The observed cross-sectional relationship could reflect a causal relationship that arises earlier in life, or confounding; additional research across the life course is warranted.     

Physical Predictors of Cognitive Performance in Healthy Older Adults: A Cross-Sectional Analysis

There is ample evidence that physical and cognitive performance are related, but the results of studies investigating this relationship show great variability. Both physical performance and cognitive performance are constructs consisting of several subdomains, but it is presently unknown if the relationship between physical and cognitive performance depends on subdomain of either construct and whether gender and age moderate this relationship. The aim of this study is to identify the strongest physical predictors of cognitive performance, to determine the specificity of these predictors for various cognitive subdomains, and to examine gender and age as potential moderators of the relationship between physical and cognitive performance in a sample of community-dwelling older adults. In total, 98 men and 122 women (average age 74.0±5.6 years) were subjected to a series of performance-based physical fitness and neuropsychological tests. Muscle strength, balance, functional reach, and walking ability (combined score of walking speed and endurance) were considered to predict cognitive performance across several domains (i.e. memory, verbal attention, visual attention, set-shifting, visuo-motor attention, inhibition and intelligence). Results showed that muscle strength was a significant predictor of cognitive performance for men and women. Walking ability and balance were significant predictors of cognitive performance for men, whereas only walking ability was significant for women. We did not find a moderating effect of age, nor did we find support for a differential effect of the physical predictors across different cognitive subdomains. In summary, our results showed a significant relationship between cognitive and physical performance, with a moderating effect of gender.     

Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline

As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning.     

What is comparable in comparative cognition?

To understand how complex, or 'advanced' various forms of cognition are, and to compare them between species for evolutionary studies, we need to understand the diversity of neural-computational mechanisms that may be involved, and to identify the genetic changes that are necessary to mediate changes in cognitive functions. The same overt cognitive capacity might be mediated by entirely different neural circuitries in different species, with a many-to-one mapping between behavioural routines, computations and their neural implementations. Comparative behavioural research needs to be complemented with a bottom-up approach in which neurobiological and molecular-genetic analyses allow pinpointing of underlying neural and genetic bases that constrain cognitive variation. Often, only very minor differences in circuitry might be needed to generate major shifts in cognitive functions and the possibility that cognitive traits arise by convergence or parallel evolution needs to be taken seriously. Hereditary variation in cognitive traits between individuals of a species might be extensive, and selection experiments on cognitive traits might be a useful avenue to explore how rapidly changes in cognitive abilities occur in the face of pertinent selection pressures.