BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study

Brain-derived neurotrophic factor (BDNF) is one of the key molecules modulating brain plasticity. While low circulating levels of BDNF have been suggested to predispose to Alzheimer's disease, very little data are available on its association with cognitive function in general population. We evaluated the association between plasma BDNF levels and cognition in a representative population sample of ageing men and women. The subjects (n=1389) were participants of the Dose-Responses to Exercise Training (DR's EXTRA) Study and represent a random sample of Eastern Finnish people (684 men and 705 women), 57-79 years of age at baseline of the study. Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery. Women had a higher mean (+/-SEM) plasma BDNF level than men (1721+/-55vs. 1495+/-54pg/ml, P<0.001). In women, 1 SD decrease in BDNF increased the risk for a low score in Naming Test by 53% (95% CI 1.21-1.92, P<0.001), in Mini-Mental State Examination by 63% (95% CI 1.21-2.20, P=0.001), in Word List Memory by 56% (95% CI 1.08-2.26, P=0.019), in Word List Recall by 50% (95% CI 1.10-2.05, P=0.010), in Word List Saving by 49% (95% CI 1.12-1.99, P=0.007), and in Word List Recognition by 64% (95% CI 1.19-2.25, P=0.002). Data were adjusted for age, education, depression, impaired glucose metabolism, cardiovascular disease, antihypertensive medication, lipid lowering medication, use of sex hormones, smoking, alcohol consumption, storing time of plasma in the freezer and platelet count. BDNF was not associated with cognition in men. Present data suggest that plasma BDNF is a biomarker of impaired memory and general cognitive function in ageing women.     

Slow gait as a motor marker of mild cognitive impairment? the relationships between functional mobility and mild cognitive impairment

The purpose of this study was to evaluate the association between functional mobility and mild cognitive impairment in older adults. A total of 800 older adults were recruited (653 controls and 147 subjects with MCI [88 subjects with aMCI and 59 subjects with naMCI]). Motor performance was measured with the Timed Up and Go test (TUG). The demographic factors associated with MCI were: age (OR = 1.05; 95% CI: 1.01–1.09) and the level of education (OR = 0.73; 95% CI: 0.68–0.79). An independent clinical factor associated with MCI was the TUG (OR = 1.14; 95% CI: 1.03–1.27). In the aMCI group, the relation between the TUG and cognitive status occurred (OR = 1.15; 95% CI: 1.02–1.31), whereas in the naMCI group this relationship was not observed. There is an association between cognitive dysfunction and impaired motor performance in older adults with MCI.     

Memory factors in Rey AVLT: Implications for early staging of cognitive decline

Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory‐Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.     

Validation of distinct amnesic and executive type memory deficit in a psychiatric sample based on retrieval performance

Studies of localized brain dysfunctions have revealed connections between patterns of cognitive dysfunction and specific profiles of memory impairment. The amnesic type of memory impairment is defined by deficits in both free recall and recognition memory, whereas the dysexecutive memory impairment is characterized by retrieval deficits, i.e. a disproportional impairment in free recall relative to recognition memory. The present study tests whether classifications of psychiatric patients into recall impaired only (= RO group) and Recall and Recognition impaired (= RR group) correspond to the executive type and amnesic type of memory impairment. The alternative hypothesis is that the two groups merely differ in degree of neuropsychological and psychiatric disturbance. Forty-four subjects impaired on California Verbal Learning Test (CVLT) were selected from a larger database of 103 impaired and non-impaired subjects with schizophrenia or recurrent major depression. Subjects were classified into RO and RR groups and compared on measures of memory strategy (recency effect and interference on CVLT), overall neuropsychological function (Stroop Test and WAIS-R similarity) and psychiatric symptom load (positive and negative symptoms). Repeated measures ANOVA showed no effects of group, i.e. the RR group did not perform consistently below the RO group with regard to memory strategy, neuropsychological function or psychiatric symptom load. Two out of three analyses showed group x test interaction, supporting the dissociation of distinct executive and amnesic profiles among psychiatric patients. The RO group was more susceptible to interference but had better recency score than the RR group. The RO had higher negative symptoms while the RR group had higher positive symptoms.     

Effects of cognitive impairment on prosodic parameters of speech production planning in multiple sclerosis

Cognitive impairment (CI) affects 40–65% of patients with multiple sclerosis (MS). CI can have a negative impact on a patient's everyday activities, such as engaging in conversations. Speech production planning ability is crucial for successful verbal interactions and thus for preserving social and occupational skills. This study investigates the effect of cognitive-linguistic demand and CI on speech production planning in MS, as reflected in speech prosody. A secondary aim is to explore the clinical potential of prosodic features for the prediction of an individual's cognitive status in MS. A total of 45 subjects, that is 22 healthy controls (HC) and 23 patients in early stages of relapsing-remitting MS, underwent neuropsychological tests probing specific cognitive processes involved in speech production planning. All subjects also performed a read speech task, in which they had to read isolated sentences manipulated as for phonological length. Results show that the speech of MS patients with CI is mainly affected at the temporal level (articulation and speech rate, pause duration). Regression analyses further indicate that rate measures are correlated with working memory scores. In addition, linear discriminant analysis shows the ROC AUC of identifying MS patients with CI is 0.70 (95% confidence interval: 0.68–0.73). Our findings indicate that prosodic planning is deficient in patients with MS-CI and that the scope of planning depends on patients’ cognitive abilities. We discuss how speech-based approaches could be used as an ecological method for the assessment and monitoring of CI in MS.     

Increasing the number of contacts generated during contact tracing interviews

ABSTRACT

To stem the spread of infectious diseases (e.g., Ebola), epidemiologists conduct contact tracing interviews (CTIs) with infected individuals regarding their contacts who may also be infected. These contact tracing interviews, however, may be vulnerable to deadly errors of omission. A promising technique to maximise recall is the Cognitive Interview (CI), which is grounded in psychological theory. In the present study, participants imagined they were infected with meningococcal meningitis and reported their contacts over the previous three days during either a control interview or a CI. To model the cognitive impairment associated with being sick, half of the participants were interviewed while simultaneously completing a cognitive impairment task. The CI generated more contacts than the control interview. However, when the cognitive impairment task was completed, the CI and the control interview performed similarly. We recommend the CI be considered as an alternative to the control interview, particularly if the interviewee is not temporarily impaired due to distraction or illness.     

The indirect effect of cognitive reserve on the relationship between age and cognition in pathological ageing: A cross-sectional retrospective study in an unselected and consecutively enrolled sample

Cognitive reserve (CR) allows individuals to maintain cognitive functionality even in the presence of pathologies. The compensation hypothesis suggests that CR plays an indirect role between age and cognitive decline, contrasting the negative effect of ageing on cognition. We test this hypothesis in an unselected and consecutively enrolled sample of memory clinic attendees (n = 134) who completed the CR Index questionnaire and three neuropsychological tests assessing global cognition (MMSE, FAB, CDT). Participants were divided into two groups based on standard diagnostic criteria (DSM-5): those who were cognitively impaired (n = 92) and those who were preserved (n = 42). A principal component analysis was used to extract a composite measure of global cognitive functioning from the three neuropsychological tests, and mediation analysis was used to examine the relationship between CR, age and global cognitive functioning in the two groups. Results revealed that: (i) age had a significant direct negative effect on the global cognitive score in both groups; (ii) the three socio-behavioural proxies of CR together suppress the direct negative relationship between age and global cognitive score in cognitively impaired patients but not in cognitively preserved participants. This study confirms the association between CR, age and cognition and allows us to validate its role in a population with cognitive impairment and extend findings to a low-to-middle educated population. These results hold important implications for public health and wellness promotion, emphasising the beneficial role of maintaining healthy and active physical, cognitive and social lifestyles.     

Does P3 Reflect Attentional or Memory Performances,or Cognition more Generally?

The study evaluated the off-line relationship of attention, memory and other cognitive performances with the auditory event-related potentials P3 (P300) and N2. The sample comprised 200 middle-aged construction workers. Verbal, visuomotor and memory tests were administered. Attentional domains were examined using CogniSpeed software. Slowed reaction times in the test of sustained attention (vigilance) were associated with delayed P3 latency (p < 0.001) and decreased P3 amplitude (p = 0.005), as well as with delayed N2 latency (p < 0.001). Visuomotor slowing in Digit Symbol was also related to delayed P3 latency (p = 0.030) and decreased P3 amplitude (p = 0.014). In contrast, mild cognitive impairment, short- and long-term memory, and concentrating or sharing attention with high working memory demands were not related to P3. The results suggest that P3 is linked to attentional performance with low working memory demands rather than to effortful working memory updating, retrieval from memory stores, or mild cognitive impairment.     

Autobiographical memory in the euthymic phase of recurrent depression

The authors investigated autobiographical memory specificity in subjects who formerly had depression. In 122 euthymic patients with at least two previous major depressive episodes, memory specificity was significantly impaired compared to matched control participants but not related to residual symptoms and illness characteristics, was not differentially affected by cognitive therapy, and was also not predictive of relapse/recurrence during the 2-year follow-up. However, memory specificity was associated with age, education, and immediate and delayed memory recall. The results suggest that memory specificity may reflect a global cognitive impairment that remains in patients who (formerly) had depression but does not constitute a trait marker for vulnerability for relapse/recurrence.     

Is Obstructive Sleep Apnoea Related to Neuropsychological Function in Healthy Older Adults? A Systematic Review and Meta-Analysis

Previous systematic reviews and meta-analyses have identified cognitive deficits in adults with obstructive sleep apnoea (OSA). However, quantitative analysis of the association between OSA and neuropsychological performance has not been conducted specifically in older adults, for whom there is a greater risk of cognitive decline. We searched Medline, Embase and PsycINFO through August 2016 for studies describing associations between OSA and neuropsychological outcomes in people aged>50 years. Meta-analyses were performed on these studies for overall cognition and within cognitive domains. Subgroup analyses were performed taking into account risk of bias and moderating differences in study design. 13 studies met eligibility criteria for analysis. A small negative association was found between OSA and all neuropsychological outcomes combined, g=0.18(95% CI 0.04–0.32), and in memory and processing speed domains. Small case-control studies from sleep clinic populations observed the greatest associations, while larger cohort studies from community samples illustrated no association. Analysis accounting for publication bias resulted in a null overall association, g=0.02 (95%CI -0.12 to 0.16). Associations between OSA and cognition in later life are highly variable and the findings differ based on the type and setting of study. It appears some older adults may be at risk of cognitive impairments attributable to OSA; however, the risk of bias renders the evidence inconclusive. High quality research is warranted in clinically diagnosed OSA patients as well as those already experiencing neuropsychological impairment and who may be regarded at higher risk of further cognitive decline.     

Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion

Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26-53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.     

Central executive involvement in children's spatial memory

Previous research with adults found that spatial short-term and working memory tasks impose similar demands on executive resources. We administered spatial short-term and working memory tasks to 8- and 11-year-olds in three separate experiments. In Experiments 1 and 2 an executive suppression task (random number generation) was found to impair performances on a short-term memory task (Corsi blocks), a working memory task (letter rotation), and a spatial visualisation task (paper folding). In Experiment 3 an articulatory suppression task only impaired performance on the working memory task. These results suggest that short-term and working memory performances are dependent on executive resources. The degree to which the short-term memory task was dependent on executive resources was expected to be related to the amount of experience children have had with such tasks. Yet we found no significant age-related suppression effects. This was attributed to differences in employment of cognitive strategies by the older children.     

Central executive involvement in children's spatial memory

Previous research with adults found that spatial short-term and working memory tasks impose similar demands on executive resources. We administered spatial short-term and working memory tasks to 8- and 11-year-olds in three separate experiments. In Experiments 1 and 2 an executive suppression task (random number generation) was found to impair performances on a short-term memory task (Corsi blocks), a working memory task (letter rotation), and a spatial visualisation task (paper folding). In Experiment 3 an articulatory suppression task only impaired performance on the working memory task. These results suggest that short-term and working memory performances are dependent on executive resources. The degree to which the short-term memory task was dependent on executive resources was expected to be related to the amount of experience children have had with such tasks. Yet we found no significant age-related suppression effects. This was attributed to differences in employment of cognitive strategies by the older children.     

Neuropsychological impairment in Parkinson's disease without dementia

Cognitive dysfunction in Parkinson's Disease (PD) has been consistently reported, but little is known about cognitive impairment in PD patients without dementia, and its association with clinical characteristics, neuropsychiatric disturbance and functional activities. Therefore, we evaluated 52 non-demented PD patients, 22 of them with mild cognitive impairment (PD-MCI) who were matched with 52 healthy controls. Our results confirm the existence of dysfunction in information processing speed, executive function, verbal memory and visuo-perceptual processing in PD. On the other hand, PD-MCI was associated with advanced age at the onset of PD, more neuropsychiatric symptoms, caregiver stress and functional problems. The study supports the hypothesis that specific neuropsychological impairments may act as modulators of functional impairment in PD, for instance slowness of information processing.     

Neuropsychological Measures that Predict Progression from Mild Cognitive Impairment to Alzheimer's type dementia in Older Adults: a Systematic Review and Meta-Analysis

This study aimed to determine the extent to which cognitive measures can predict progression from mild cognitive impairment (MCI) to Alzheimer’s type dementia (AD), assess the predictive accuracy of different cognitive domain categories, and determine whether accuracy varies as a function of age and length of follow-up. We systematically reviewed and meta-analyzed data from longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will develop AD. We searched articles in Medline, Cochrane, EMBASE, PsycINFO, and the Web of Science. Methodological quality was assessed using the STARDem and QUADAS standards. Twenty-eight studies met the eligibility criteria (2365 participants) and reported predictive values from 61 neuropsychological tests with a 31-month mean follow-up. Values were pooled to provide combined accuracy for 14 cognitive domains. Many domains showed very good predictive accuracy with high sensitivity and specificity values (≥ 0.7). Verbal memory measures and many language tests yielded very high predictive accuracy. Other domains (e.g., executive functions, visual memory) showed better specificity than sensitivity. Predictive accuracy was highest when combining memory measures with a small set of other domains or when relying on broad cognitive batteries. Cognitive tests are excellent at predicting MCI individuals who will progress to dementia and should be a critical component of any toolkit intended to identify AD at the pre-dementia stage. Some tasks are remarkable as early indicators, whereas others might be used to suggest imminent progression.     

大学毕业生就业能力、求职认知评价、就业不安全感对心理健康预测作用的追踪研究

旨在探究大学毕业生就业能力对求职过程中心理健康的预测作用,以及求职认知评价和就业不安全感在其中的中介作用。采用结构方程模型等对343个样本的三轮追踪问卷调查数据进行分析后发现：就业能力显著正向预测心理健康;挑战认知评价和就业不安全感依次中介就业能力对心理健康的预测作用。研究结果表明,可以通过提高大学毕业生就业能力来积极促进其对求职的正确认知评价,从而纾解就业不安全感,保持和改善求职过程中的心理健康状况。     

Working memory and attention are still impaired after three years in patients with stress‐related exhaustion

Cognitive impairment is one of the most pronounced symptoms reported by patients with stress‐related mental health problems. Impairments related to executive function and to some extent speed and attention are therefore common in patients with stress‐related burnout/exhaustion. In this paper we present a follow‐up of cognitive performance in patients with stress‐related exhaustion several years after they initially sought medical care. Thirty patients and 27 healthy controls, mean age 49 years (SD 6.5) and 55 years (SD 6.7) respectively, were included, all of whom had undergone baseline measurements of neuropsychological functioning. The mean follow‐up time was three years. Half of the patients still reported mental health problems at follow‐up and over time no major changes in cognitive performance were noted. The patients still performed significantly poorer than controls with regard to cognitive functions, mainly related to speed, attention and memory function. Long‐lasting impairment of cognitive functions related to speed, attention and memory function noted in patients with stress‐related exhaustion should be acknowledged and taken into consideration during treatment and when discussing a return to work. Follow‐up periods longer than three years are needed to explore the persistence of the cognitive impairment.     

Motivational reserve: motivation-related occupational abilities and risk of mild cognitive impairment and Alzheimer disease

Midlife motivational abilities, that is, skills to initiate and persevere in the implementation of goals, have been related to mental and physical health, but their association with risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD) has not yet been directly investigated. This relation was examined with data from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). A total of 3,327 nondemented participants (50.3% of a randomly selected sample) aged 75-89 years were recruited in primary care and followed up twice (after 1.5 and 3 years). Motivation-related occupational abilities were estimated on the basis of the main occupation (assessed at follow-up II) using the Occupational Information Network (O* NET) database, which provides detailed information on worker characteristics and abilities. Cox proportional hazards models were used to evaluate the relative risk of developing MCI and AD in relation to motivation-related occupational abilities, adjusting for various covariates. Over the 3 years of follow-up, 15.2% participants developed MCI and 3.0% developed AD. In a fully adjusted model, motivation-related occupational abilities were found to be associated with a reduced risk of MCI (HR: 0.77; 95% CI: 0.64-0.92). Motivation-related occupational abilities were associated with reduced risk of AD in ApoE ε4 carriers (HR: 0.48; CI: 0.25-0.91), but not in noncarriers (HR: 0.99; CI: 0.65-1.53). These results suggest that midlife motivational abilities are associated with reduced risk of MCI in general and with reduced risk of AD in ApoE ε4 carriers. Revealing the mechanisms underlying this association may inform novel prevention strategies for decelerating cognitive decline in old age.     

The importance of impaired physical health and age in normal cognitive aging

The objective of this study was to investigate the importance of impaired physical health and age in normal cognitive aging. In our cross-sectional, clinical and explorative study, medical and neuropsychological data from 118 voluntary healthy controls aged 26-91 years were collected from five recruitment occasions. Health was assessed according to a criterion reflecting clinical and subclinical severity. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological assessment. Regression analyses showed a significant incidence of clinical and subclinical medical disorders that explained 10.8% of the variation in cognitive performance, while age-related impairment explained 5.6%. Findings of the central nervous system were important but various other medical findings explained about half of the health-related variation. Cognitively demanding tasks were more susceptible to impaired physical health while tasks comprising salient motor- and visual spatial elements were more prone to be impaired by age. Our findings suggest (1) that impaired physical health is more important than chronological age in accounting for cognitive impairment across the adult lifespan, (2) that age and health dissociate with regard to cognitive functions affected, and (3) that selection for so-called "super healthy" elderly people might be justified in cognitive research. Because the prevalent diseases in normal aging are potentially preventable, the present findings promise good prospect for prevention of future cognitive disability among elderly people.     

Encountering the Body at the Site of the Suicide: A Population‐Based Survey in Sweden

Encountering the body of a child who died by suicide at the site of death is believed to be especially harmful for bereaved parents. We investigated the association between encountering the body at the site of the suicide and psychological distress in 666 suicide‐bereaved parents. Parents who had encountered their child's body at the site of the suicide (n = 147) did not have a higher risk of nightmares (relative risk [RR] 0.95, 95% confidence interval [CI] 0.67–1.35), intrusive memories (RR 0.97, 95% CI 0.84–1.13), avoidance of thoughts (RR 0.97, 95% CI 0.74–1.27), avoidance of places or things (RR 0.91, 95% CI 0.66–1.25), anxiety (RR 0.93, 95% CI 0.64–1.33), or depression (RR 0.94, 95% CI 0.63–1.42) compared with parents who had not encountered the body (n = 512). Our results suggest that losing a child by suicide is sufficiently disastrous by itself to elicit posttraumatic responses or psychiatric morbidity whether or not the parent has encountered the deceased child at the site of death.