Age-Correlated Gene Expression in Normal and Neurodegenerative Human Brain Tissues

Background

Human brain aging has received special attention in part because of the elevated risks of neurodegenerative disorders such as Alzheimer''s disease in seniors. Recent technological advances enable us to investigate whether similar mechanisms underlie aging and neurodegeneration, by quantifying the similarities and differences in their genome-wide gene expression profiles.

Principal Findings

We have developed a computational method for assessing an individual''s “physiological brain age” by comparing global mRNA expression datasets across a range of normal human brain samples. Application of this method to brains samples from select regions in two diseases – Alzheimer''s disease (AD, superior frontal gyrus), frontotemporal lobar degeneration (FTLD, in rostral aspect of frontal cortex ∼BA10) – showed that while control cohorts exhibited no significant difference between physiological and chronological ages, FTLD and AD exhibited prematurely aged expression profiles.

Conclusions

This study establishes a quantitative scale for measuring premature aging in neurodegenerative disease cohorts, and it identifies specific physiological mechanisms common to aging and some forms of neurodegeneration. In addition, accelerated expression profiles associated with AD and FTLD suggest some common mechanisms underlying the risk of developing these diseases.     

Cognitive alterations in motor imagery process after left hemispheric ischemic stroke

Background

Motor imagery training is a promising rehabilitation strategy for stroke patients. However, few studies had focused on the neural mechanisms in time course of its cognitive process. This study investigated the cognitive alterations after left hemispheric ischemic stroke during motor imagery task.

Methodology/Principal Findings

Eleven patients with ischemic stroke in left hemisphere and eleven age-matched control subjects participated in mental rotation task (MRT) of hand pictures. Behavior performance, event-related potential (ERP) and event-related (de)synchronization (ERD/ERS) in beta band were analyzed to investigate the cortical activation. We found that: (1) The response time increased with orientation angles in both groups, called “angle effect”, however, stoke patients’ responses were impaired with significantly longer response time and lower accuracy rate; (2) In early visual perceptual cognitive process, stroke patients showed hypo-activations in frontal and central brain areas in aspects of both P200 and ERD; (3) During mental rotation process, P300 amplitude in control subjects decreased while angle increased, called “amplitude modulation effect”, which was not observed in stroke patients. Spatially, patients showed significant lateralization of P300 with activation only in contralesional (right) parietal cortex while control subjects showed P300 in both parietal lobes. Stroke patients also showed an overall cortical hypo-activation of ERD during this sub-stage; (4) In the response sub-stage, control subjects showed higher ERD values with more activated cortical areas particularly in the right hemisphere while angle increased, named “angle effect”, which was not observed in stroke patients. In addition, stroke patients showed significant lower ERD for affected hand (right) response than that for unaffected hand.

Conclusions/Significance

Cortical activation was altered differently in each cognitive sub-stage of motor imagery after left hemispheric ischemic stroke. These results will help to understand the underlying neural mechanisms of mental rotation following stroke and may shed light on rehabilitation based on motor imagery training.     

The Shape Trail Test: Application of a New Variant of the Trail Making Test

Objective

The Trail making test (TMT) is culture-loaded because of reliance on the Latin alphabet, limiting its application in Eastern populations. The Shape Trail Test (STT) has been developed as a new variant. This study is to examine the applicability of the STT in a senile Chinese population and to evaluate its potential advantages and disadvantages.

Method

A total of 2470 participants were recruited, including 1151 cognitively normal control (NC), 898 amnestic mild cognitive impairment (aMCI), and 421 mild Alzheimer disease (AD) patients. Besides the STT, the Mini mental state examination and a comprehensive neuropsychological battery involving memory, language, attention, executive function and visuospatial ability were administered to all the participants. In a subgroup of 100 NC and 50 AD patients, both the STT and the Color Trail Test (CTT) were performed.

Results

In NC, the time consumed for Part A and B (STT-A and STT-B) significantly correlated with age and negatively correlated with education (p<0.01). STT-A and B significantly differed among the AD, aMCI and NC. The number that successfully connected within one minute in Part B (STT-B-1 min) correlated well with STT-B (r = 0.71, p<0.01) and distinguished well among NC, aMCI and AD. In the receiver operating characteristic curve analysis, the AUCs (area under the curve) for STT-A, STT-B, and STT-B-1min in identifying AD were 0.698, 0.694 and 0.709, respectively. The STT correlated with the CTT, but the time for completion was longer.

Conclusion

The TMT is a sensitive test of visual search and sequencing. The STT is a meaningful attempt to develop a “culture-fair” variant of the TMT in addition to the CTT.     

Prevalence and Correlates of Common Mental Disorders among Mothers of Young Children in Kilimanjaro Region of Tanzania

Background

Although poor maternal mental health is a major public health problem, with detrimental effects on the individual, her children and society, information on its correlates in low-income countries is sparse.

Aims

This study investigates the prevalence of common mental disorders (CMD) among at-risk mothers, and explores its associations with sociodemographic factors.

Methods

This population-based survey of mothers of children aged 0–36 months used the 14-item Shona Symptom Questionnaire (SSQ). Mothers whose response was “yes” to 8 or more items on the scale were defined as “at risk of CMD.”

Results

Of the 1,922 mothers (15–48 years), 28.8% were at risk of CMD. Risk of CMD was associated with verbal abuse, physical abuse, a partner who did not help with the care of the child, being in a polygamous relationship, a partner with low levels of education, and a partner who smoked cigarettes. Cohabiting appeared to be protective.

Conclusions

Taken together, our results indicate the significance of the quality of relations with one’s partner in shaping maternal mental health. The high proportion of mothers who are at risk of CMD emphasizes the importance of developing evidence-based mental health programmes as part of the care package aimed at improving maternal well-being in Tanzania and other similar settings.     

APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD

Objectives

To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer''s disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.

Methods

MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.

Results

Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.

Conclusions

These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.     

Perceptual Other-Race Training Reduces Implicit Racial Bias

Background

Implicit racial bias denotes socio-cognitive attitudes towards other-race groups that are exempt from conscious awareness. In parallel, other-race faces are more difficult to differentiate relative to own-race faces – the “Other-Race Effect.” To examine the relationship between these two biases, we trained Caucasian subjects to better individuate other-race faces and measured implicit racial bias for those faces both before and after training.

Methodology/Principal Findings

Two groups of Caucasian subjects were exposed equally to the same African American faces in a training protocol run over 5 sessions. In the individuation condition, subjects learned to discriminate between African American faces. In the categorization condition, subjects learned to categorize faces as African American or not. For both conditions, both pre- and post-training we measured the Other-Race Effect using old-new recognition and implicit racial biases using a novel implicit social measure – the “Affective Lexical Priming Score” (ALPS). Subjects in the individuation condition, but not in the categorization condition, showed improved discrimination of African American faces with training. Concomitantly, subjects in the individuation condition, but not the categorization condition, showed a reduction in their ALPS. Critically, for the individuation condition only, the degree to which an individual subject''s ALPS decreased was significantly correlated with the degree of improvement that subject showed in their ability to differentiate African American faces.

Conclusions/Significance

Our results establish a causal link between the Other-Race Effect and implicit racial bias. We demonstrate that training that ameliorates the perceptual Other-Race Effect also reduces socio-cognitive implicit racial bias. These findings suggest that implicit racial biases are multifaceted, and include malleable perceptual skills that can be modified with relatively little training.     

Prevalence of Alzheimer’s Pathologic Endophenotypes in Asymptomatic and Mildly Impaired First-Degree Relatives

Objective

A positive family history (FH) is a risk factor for late-onset Alzheimer’s disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum.

Design

Cross-sectional analyses of data from a national biomarker study.

Setting

The Alzheimer’s Disease Neuroimaging Initiative national study.

Patients

257 subjects (ages 55–89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data.

Outcome Measures

Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes.

Statistics

Univariate and multivariate analyses.

Results

In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH− subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited “pathologic signature of AD” (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH− controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH− subjects in any group.

Conclusions

A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.     

Early-Stage Psychotherapy Produces Elevated Frontal White Matter Integrity in Adult Major Depressive Disorder

Background

Psychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter.

Methods

Twenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis.

Results

Post-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe.

Conclusions

At an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the “top-down” mechanism of psychotherapy.     

Right Anterior Insula: Core Region of Hallucinations in Cognitive Neurodegenerative Diseases

Objectives

We investigated the neural basis of hallucinations Alzheimer''s disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.

Methods

AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. “Core regions” (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.

Results

Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).

Conclusion

Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.     

Relative Influence of Genetics and Shared Environment on Child Mental Health Symptoms Depends on Comorbidity

Background

Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.

Methods

The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).

Results

Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes.

Conclusions

We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated.     

Mental Health Literacy of Depression: Gender Differences and Attitudinal Antecedents in a Representative British Sample

Background

Poor mental health literacy and negative attitudes toward individuals with mental health disorders may impede optimal help-seeking for symptoms of mental ill-health. The present study examined the ability to recognize cases of depression as a function of respondent and target gender, as well as individual psychological differences in attitudes toward persons with depression.

Methods

In a representative British general population survey, the ability to correctly recognize vignettes of depression was assessed among 1,218 adults. Respondents also rated the vignettes along a number of attitudinal dimensions and completed measures of attitudes toward seeking psychological help, psychiatric skepticism, and anti-scientific attitudes.

Results

There were significant differences in the ability to correctly identify cases of depression as a function of respondent and target gender. Respondents were more likely to indicate that a male vignette did not suffer from a mental health disorder compared to a female vignette, and women were more likely than men to indicate that the male vignette suffered from a mental health disorder. Attitudes toward persons with depression were associated with attitudes toward seeking psychological help, psychiatric skepticism, and anti-scientific attitudes.

Conclusion

Initiatives that consider the impact of gender stereotypes as well as individual differences may enhance mental health literacy, which in turn is associated with improved help-seeking behaviors for symptoms of mental ill-health.     

Cognitive Decline in Patients with Alzheimer’s Disease and Its Related Factors in a Memory Clinic Setting,Shanghai, China

Objectives

Progressive cognitive decline is a characteristic hallmark of AD. It is important to identify prognostic markers to improve patient care and long-term planning. We aimed to identify the characteristics of disease progression in AD patients, focusing on cognitive decline and its related factors.

Methods

Clinically diagnosed AD patients in a memory clinic were followed. The mini–mental state examination (MMSE) and a battery of other neuropsychological tests were performed to assess the rate of cognitive decline and to analyze the related factors.

Results

A total of 165 AD patients were analyzed for cognitive changes. The MMSE scores declined at a rate of 1.52 points per year. Most neuropsychological test scores deteriorated significantly over time. Younger and early-onset AD patients deteriorated more rapidly than older and late-onset patients in global cognition and executive function. Men declined faster in memory but slower in attention than women. Higher education was associated with more rapid deterioration in visuo-spatial ability. Family history, hypertension and cerebral vascular disease were also associated with disease progression.

Conclusion

Attention, executive and visuo-spatial functions deteriorate at faster rates than other cognitive functions in AD patients. Age and age at onset were the main factors that associated with deterioration.     

Prolonged visual experience in adulthood modulates holistic face perception

Background

Using the well-known composite illusion as a marker of the holistic perception of faces, we tested how prolonged visual experience with a specific population of faces (4- to 6-year-old children) modulates the face perception system in adulthood.

Methodology/Principal Findings

We report a face composite effect that is larger for adult than children faces in a group of adults without experience with children faces (“children-face novices”), while it is of equal magnitude for adults and children faces in a population of preschool teachers (“children-face experts”). When considering preschool teachers only, we observed a significant correlation between the number of years of experience with children faces and the differential face composite effect between children and adults faces. Participants with at least 10 years of qualitative experience with children faces had a larger composite face effect for children than adult faces.

Conclusions/Significance

Overall, these observations indicate that even in adulthood face processes can be reshaped qualitatively, presumably to facilitate efficient processing of the differential morphological features of the frequently encountered population of faces.     

Modeling the Building Blocks of Biodiversity

Background

Networks of single interaction types, such as plant-pollinator mutualisms, are biodiversity’s “building blocks”. Yet, the structure of mutualistic and antagonistic networks differs, leaving no unified modeling framework across biodiversity’s component pieces.

Methods/Principal Findings

We use a one-dimensional “niche model” to predict antagonistic and mutualistic species interactions, finding that accuracy decreases with the size of the network. We show that properties of the modeled network structure closely approximate empirical properties even where individual interactions are poorly predicted. Further, some aspects of the structure of the niche space were consistently different between network classes.

Conclusions/Significance

These novel results reveal fundamental differences between the ability to predict ecologically important features of the overall structure of a network and the ability to predict pair-wise species interactions.     

Structural MRI in Frontotemporal Dementia: Comparisons between Hippocampal Volumetry,Tensor-Based Morphometry and Voxel-Based Morphometry

Background

MRI is an important clinical tool for diagnosing dementia-like diseases such as Frontemporal Dementia (FTD). However there is a need to develop more accurate and standardized MRI analysis methods.

Objective

To compare FTD with Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) with three automatic MRI analysis methods - Hippocampal Volumetry (HV), Tensor-based Morphometry (TBM) and Voxel-based Morphometry (VBM), in specific regions of interest in order to determine the highest classification accuracy.

Methods

Thirty-seven patients with FTD, 46 patients with AD, 26 control subjects, 16 patients with progressive MCI (PMCI) and 48 patients with stable MCI (SMCI) were examined with HV, TBM for shape change, and VBM for gray matter density. We calculated the Correct Classification Rate (CCR), sensitivity (SS) and specificity (SP) between the study groups.

Results

We found unequivocal results differentiating controls from FTD with HV (hippocampus left side) (CCR = 0.83; SS = 0.84; SP = 0.80), with TBM (hippocampus and amygdala (CCR = 0.80/SS = 0.71/SP = 0.94), and with VBM (all the regions studied, especially in lateral ventricle frontal horn, central part and occipital horn) (CCR = 0.87/SS = 0.81/SP = 0.96). VBM achieved the highest accuracy in differentiating AD and FTD (CCR = 0.72/SS = 0.67/SP = 0.76), particularly in lateral ventricle (frontal horn, central part and occipital horn) (CCR = 0.73), whereas TBM in superior frontal gyrus also achieved a high accuracy (CCR = 0.71/SS = 0.68/SP = 0.73). TBM resulted in low accuracy (CCR = 0.62) in the differentiation of AD from FTD using all regions of interest, with similar results for HV (CCR = 0.55).

Conclusion

Hippocampal atrophy is present not only in AD but also in FTD. Of the methods used, VBM achieved the highest accuracy in its ability to differentiate between FTD and AD.     

Aberrant Default Mode Functional Connectivity in Early Onset Schizophrenia

Background

The default mode network (DMN) has been linked to a number of mental disorders including schizophrenia. However, the abnormal connectivity of DMN in early onset schizophrenia (EOS) has been rarely reported.

Methods

Independent component analysis (ICA) was used to investigate functional connectivity (FC) of the DMN in 32 first-episode adolescents with EOS and 32 age and gender-matched healthy controls.

Results

Compared to healthy controls, patients with EOS showed increased FC between the medial frontal gyrus and other areas of the DMN. Partial correlation analyses showed that the FC of medial frontal gyrus significantly correlated with PANSS-positive symptoms (partial correlation coefficient  = 0.538, Bonferoni corrected P = 0.018).

Limitations

Although the sample size of participants was comparable with most fMRI studies to date, it was still relatively small. Pediatric brains were registered to the MNI adult brain template. However, possible age-specific differences in spatial normalization that arise from registering pediatric brains to the MNI adult brain template may have little effect on fMRI results.

Conclusion

This study provides evidence for functional abnormalities of DMN in first-episode EOS. These abnormalities could be a source of abnormal introspectively-oriented mental actives.     

Temporomandibular Disorders: The Habitual Chewing Side Syndrome

Background

Temporomandibular disorders are the most common cause of chronic orofacial pain, but, except where they occur subsequent to trauma, their cause remains unknown. This cross-sectional study assessed chewing function (habitual chewing side) and the differences of the chewing side and condylar path and lateral anterior guidance angles in participants with chronic unilateral temporomandibular disorder. This is the preliminary report of a randomized trial that aimed to test the effect of a new occlusal adjustment therapy.

Methods

The masticatory function of 21 randomly selected completely dentate participants with chronic temporomandibular disorders (all but one with unilateral symptoms) was assessed by observing them eat almonds, inspecting the lateral horizontal movement of the jaw, with kinesiography, and by means of interview. The condylar path in the sagittal plane and the lateral anterior guidance angles with respect to the Frankfort horizontal plane in the frontal plane were measured on both sides in each individual.

Results

Sixteen of 20 participants with unilateral symptoms chewed on the affected side; the concordance (Fisher’s exact test, P = .003) and the concordance-symmetry level (Kappa coefficient κ = 0.689; 95% confidence interval [CI], 0.38 to 0.99; P = .002) were significant. The mean condylar path angle was steeper (53.47(10.88) degrees versus 46.16(7.25) degrees; P = .001), and the mean lateral anterior guidance angle was flatter (41.63(13.35) degrees versus 48.32(9.53) degrees P = .036) on the symptomatic side.

Discussion

The results of this study support the use of a new term based on etiology, “habitual chewing side syndrome”, instead of the nonspecific symptom-based “temporomandibular joint disorders”; this denomination is characterized in adults by a steeper condylar path, flatter lateral anterior guidance, and habitual chewing on the symptomatic side.     

Non-Listening and Self Centered Leadership – Relationships to Socioeconomic Conditions and Employee Mental Health

Background

The way in which leadership is experienced in different socioeconomic strata is of interest per se, as well as how it relates to employee mental health.

Methods

Three waves of SLOSH (Swedish Longitudinal Occupational Survey of Health, a questionnaire survey on a sample of the Swedish working population) were used, 2006, 2008 and 2010 (n = 5141). The leadership variables were: “Non-listening leadership” (one question: “Does your manager listen to you?” - four response categories), “Self centered leadership” (sum of three five-graded questions – “non-participating”, “asocial” and “loner”). The socioeconomic factors were education and income. Emotional exhaustion and depressive symptoms were used as indicators of mental health.

Results

Non-listening leadership was associated with low income and low education whereas self-centered leadership showed a weaker relationship with education and no association at all with income. Both leadership variables were significantly associated with emotional exhaustion and depressive symptoms. “Self centered” as well as “non-listening” leadership in 2006 significantly predicted employee depressive symptoms in 2008 after adjustment for demographic variables. These predictions became non-significant when adjustment was made for job conditions (demands and decision latitude) in the “non-listening” leadership analyses, whereas predictions of depressive symptoms remained significant after these adjustments in the “self-centered leadership” analyses.

Conclusions

Our results show that the leadership variables are associated with socioeconomic status and employee mental health. “Non-listening” scores were more sensitive to societal change and more strongly related to socioeconomic factors and job conditions than “self-centered” scores.     

Memory Concerns,Memory Performance and Risk of Dementia in Patients with Mild Cognitive Impairment

Background

Concerns about worsening memory (“memory concerns”; MC) and impairment in memory performance are both predictors of Alzheimer''s dementia (AD). The relationship of both in dementia prediction at the pre-dementia disease stage, however, is not well explored. Refined understanding of the contribution of both MC and memory performance in dementia prediction is crucial for defining at-risk populations. We examined the risk of incident AD by MC and memory performance in patients with mild cognitive impairment (MCI).

Methods

We analyzed data of 417 MCI patients from a longitudinal multicenter observational study. Patients were classified based on presence (n = 305) vs. absence (n = 112) of MC. Risk of incident AD was estimated with Cox Proportional-Hazards regression models.

Results

Risk of incident AD was increased by MC (HR = 2.55, 95%CI: 1.33–4.89), lower memory performance (HR = 0.63, 95%CI: 0.56–0.71) and ApoE4-genotype (HR = 1.89, 95%CI: 1.18–3.02). An interaction effect between MC and memory performance was observed. The predictive power of MC was greatest for patients with very mild memory impairment and decreased with increasing memory impairment.

Conclusions

Our data suggest that the power of MC as a predictor of future dementia at the MCI stage varies with the patients'' level of cognitive impairment. While MC are predictive at early stage MCI, their predictive value at more advanced stages of MCI is reduced. This suggests that loss of insight related to AD may occur at the late stage of MCI.