Christina Degen

Neurological Soft Signs in the Clinical Course of Schizophrenia: Results of a Meta-Analysis

Neurological soft signs (NSS) comprise subtle deficits in sensory integration, motor coordination, and sequencing of complex motor acts, which are typically observed in the majority of schizophrenia patients, including chronic cases and neuroleptic-naïve first-episode patients. However, recent studies clearly demonstrate that NSS are not a static feature of schizophrenia but vary in the clinical course of the disorder. This effect was investigated in a meta-analysis based on 17 longitudinal studies published between 1992 and 2012. Studies included between 10 and 93 patients with schizophrenia spectrum disorders (total number 787) with follow-up periods between 2 and 208 weeks. Beside the Neurological Examination Scale, the Cambridge Neurological Inventory and the Heidelberg NSS Scale were used to assess NSS. All but three studies found NSS to decrease in parallel with remission of psychopathological symptoms. This effect was more pronounced in patients with a remitting compared to a non-remitting, chronic course (Cohen’s d 0.81 vs. 0.15) and was significantly correlated with length of the follow-up period (r = −0.64) but not with age (r = 0.28). NSS scores did not decrease to the level typically observed in healthy controls. From a clinical perspective, NSS may therefore be used to identify subjects at risk to develop schizophrenia and to monitor disease progression.

Comparison of automated brain segmentation using a brain phantom and patients with early Alzheimer's dementia or mild cognitive impairment.

Magnetic resonance imaging (MRI) and brain volumetry allow for the quantification of changes in brain volume using automatic algorithms which are widely used in both, clinical and scientific studies. However, studies comparing the reliability of these programmes are scarce and mainly involved MRI derived from younger healthy controls. This study evaluates the reliability of frequently used segmentation programmes (SPM, FreeSurfer, FSL) using a realistic digital brain phantom and MRI brain acquisitions from patients with manifest Alzheimers disease (AD, n=34), mild cognitive impairment (MCI, n=60), and healthy subjects (n=32) matched for age and sex. Analysis of the brain phantom dataset demonstrated that SPM, FSL and FreeSurfer underestimate grey matter and overestimate white matter volumes with increasing noise. FreeSurfer calculated overall smaller brain volumes with increasing noise. Image inhomogeneity had only minor, non- significant effects on the results obtained with SPM and FreeSurfer 5.1, but had effects on the FSL results (increased white matter volumes with decreased grey matter volumes). The analysis of the patient data yielded decreasing volumes of grey and white matter with progression of brain atrophy independent of the method used. FreeSurfer calculated the largest grey matter and the smallest white matter volumes. FSL calculated the smallest grey matter volumes; SPM the largest white matter volumes. Best results are obtained with good image quality. With poor image quality, especially noise, SPM provides the best segmentation results. An optimised template for segmentation had no significant effect on segmentation results. While our findings underline the applicability of the programmes investigated, SPM may be the programme of choice when MRIs with limited image quality or brain images of elderly should be analysed.

Neurological Soft Signs in Aging, Mild Cognitive Impairment, and Alzheimer’s Disease – The Impact of Cognitive Decline and Cognitive Reserve

Objectives: Neurological soft signs (NSS), i.e., minor motor and sensory changes, are a common feature in severe psychiatric disorders. We sought to establish the frequency of NSS in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) on basis of a large population-based sample and to identify their neuropsychological correlates including cognitive reserve. Methods: Neurological soft signs were examined using an abbreviated version of the Heidelberg NSS Scale in 221 “old” participants born between 1930 and 1932 (63 with MCI, 15 with AD, 143 healthy old controls) and 256 healthy “young” participants (born between 1950 and 1952) of the population-based interdisciplinary longitudinal study of aging. Subjects received thorough neuropsychological testing; years of school education were used as a proxy for cognitive reserve. Results: Neurological soft signs scores were significantly (p < 0.001) higher in the AD patients (5.6 ± 3.11) than in the healthy old controls (2.8 ± 1.90) and in the MCI patients (3.0 ± 1.96). This result was confirmed after years of school education, which were inversely correlated (r = −0.25; p < 0.001) with NSS were entered as a covariate. In the patients, but not in the controls, NSS were significantly correlated with deficits in executive functioning and visuospatial functioning. Comparison of NSS scores between “old” (2.84 ± 1.9) and “young” (2.46 ± 1.97) controls yielded only minor, non-significant differences after education (13.86 ± 3.0 vs. 14.61 ± 2.48 years, respectively) was controlled for. Conclusion: Our results demonstrate that NSS are frequently found in mild AD, but not in MCI. NSS refer to frontal-executive deficits and visuospatial dysfunction rather than age per se and can be partly compensated for by cognitive reserve.

Neuropsychological profiles and verbal abilities in lifelong bilinguals with mild cognitive impairment and Alzheimer's disease.

Bilingualism is associated with enhanced executive functioning and delayed onset of mild cognitive impairment (MCI) and Alzheimers disease (AD). Here, we investigated neuropsychological differences between mono- and bilingual patients with MCI and AD as well as the respective effects of dementia on the dominant and non-dominant language of bilinguals. 69 patients with MCI (n = 22) or AD (n = 47) and 17 healthy controls were included. 41 subjects were classified as lifelong bilinguals (mean age: 73.6; SD = 11.5) and 45 as monolinguals (mean age: 78.1; SD = 10.9). Neuropsychological performance was assessed on the CERAD-NP, the clock-drawing test, and the logical memory subscale of the Wechsler Memory Scale. Neuropsychological profiles showed only minor nonsignificant differences between mono- and bilingual subjects when compared between diagnostic groups. Bilingual MCI patients scored significantly lower on the verbal fluency and picture naming task in their dominant language than bilingual controls. Bilingual AD patients showed a reduced performance in their nondominant language when compared to bilingual MCI patients and bilingual controls (main effect language dominance: verbal fluency task p < 0.001; BNT p < 0.001). Bilingual MCI and AD patients show a similar pattern of neuropsychological deficits as monolingual patients do. The dominant language appears to be compromised first in bilingual MCI patients, while severe deficits of the nondominant language develop later in the course with manifestation of AD. These findings are important for the diagnostic work up of bilingual patients and the development of improved care concepts for bilingual patients such as migrant populations.

Training-induced cerebral changes in the elderly

As the demographic shift towards an aging population prevails, the improvement and/or maintenance of cognitive functioning appear increasingly important. To date, the effectiveness of cognitive, cardiovascular and sensorimotor training approaches in older adults has been demonstrated frequently using neuropsychological and behavioral performance measures. We present an overview of selected studies applying modern imaging techniques (fMRI, PET) to assess practice-induced structural and functional changes in the brain. Structurally, practice is associated with volumetric increases. Functionally, reorganization of neural network recruitment, overall decreases and increases in activity levels are found. Thus, the human brain retains a high degree of plasticity in old age. Moreover, it seems that practice leads to more efficient processing, requiring less neural engagement to perform the same task. While the concept of economization finds widespread support in healthy populations, in patient groups this effect has proven to be absent or reversed. The concept of cognitive reserve and potentially compensatory mechanisms are discussed in this context.

Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease

While diabetes mellitus (DM) Type II has repeatedly been linked to Alzheimer´s disease (AD) and mild cognitive impairment (MCI), longitudinal research is scarce and disease duration has not always been taken into account. In a birth cohort born between 1930 and 1932 we investigated the influence of DM Type II and disease duration on neuropsychological functioning (memory/learning, attention, verbal fluency, visuospatial thinking and abstract thinking) across 14 years. Subjects who developed MCI or AD performed significantly poorer on all neuropsychological tests applied. While significant main effects DM Type II did not arise, its presence led to a significant deterioration of performance in the digit symbol test and visuospatial thinking over time. Additionally, in visuospatial thinking this change was more pronounced for individuals suffering from MCI/AD. We found that, as a concomitant disease DM Type II does not affect memory functioning, which is typically compromised in MCI and early AD. Rather, it may lead to deficits in cognitive flexibility and visuospatial thinking. DM Type II can be considered a frequent comorbid condition which can aggravate the course of MCI and AD. In this respect it may serve as a model for other comorbid conditions in AD.

Improving Stock-Flow Reasoning With Verbal Formats

Background. Stock-flow (SF) problems are ubiquitous in nature, ranging from the accumulation of water in a tub to the accumulation of CO2 in the atmosphere. However, research on SF failure repeatedly demonstrates that people have severe difficulties understanding even the most basic SF problems. Purpose. This study tested the hypothesis that people’s understanding of SF problems depends on the presentation format used. Specifically, we expect SF failure to decrease when avoiding previously used scientific formats comprising coordinate systems and graphs, and SF problems are presented in verbal formats. Method. Participants (N = 107) solved a range of different SF problems with experimentally varied presentation formats (verbal vs. graphic). We assessed fundamental understanding of graphs and graphical versus verbal production of stocks and in- and outflows. Results. Solution rates show that (a) SF failure is at least partially caused by specifics of the presentation format used previously; (b) fundamental misunderstandings in the construction of graphs can explain previous findings; and (c) the majority of participants arrived at the correct solution when SF problems were presented verbally. Conclusion. The present study indicates that people are able to solve SF problems when they are presented in accessible formats. This result bears implications for simulation-based learning and assessment, and for the communication of SF problems.

Bilingualism as a Contributor to Cognitive Reserve? Evidence from Cerebral Glucose Metabolism in Mild Cognitive Impairment and Alzheimer’s Disease

Objective Bilingualism is discussed as one factor contributing to “cognitive reserve” (CR), as it enhances executive control functions. To elucidate the underlying cerebral correlates, regional glucose uptake was compared between bilinguals and monolinguals with mild cognitive impairment (MCI) and beginning-stage Alzheimer’s disease (AD) by using [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Methods Thirty patients (73.2 ± 7.4) diagnosed with MCI or probable AD received physical and neuropsychological examinations, blood tests, and FDG-PET scans. Sixteen patients were classified as lifelong bilinguals, following the criterion of Bialystok et al., and groups were matched for age, sex, and mini mental state examination scores. Analyses were conducted using statistical parametric mapping version 8. The whole brain was used as reference region for intensity normalization and years of education were controlled for. Results Bilingual patient groups showed substantially greater impairment of glucose uptake in frontotemporal and parietal regions [including Brodmann areas (BAs) 9, 47, 40, and 21] and in the left cerebellum relative to monolingual patients. Conclusion Bilingualism is likely to contribute to CR, given that bilingual patients showed more severe brain changes than monolinguals when adjusting for severity of cognitive impairment. The latter did not only comprise BAs relevant to speech and language but also structures typically involved in AD pathology, such as the temporal and the parietal cortices.

The COMTp.Val158Met Polymorphism and Cognitive Performance in Adult Development, Healthy Aging and Mild Cognitive Impairment.

Background: The impact of genetic polymorphisms on cognition is assumed to increase with age as losses of brain resources have to be compensated for. We investigate the relation of catechol-O-methyltransferase (COMT)p.Val158Met polymorphism and cognitive capacity in the course of adult development, healthy aging and the development of mild cognitive impairment (MCI) in two birth cohorts of subjects born between 1930 and 1932 or between 1950 and 1952. Methods: Thorough neuropsychological assessment was conducted in a total of 587 participants across three examination waves between 1993 and 2008. The COMT genotype was determined as a restriction fragment length polymorphism after PCR amplification and digestion with NlaIII. Results: Significant effects of the COMTp.Val158Met polymorphism were identified for attention and cognitive flexibility in the younger but not the older cohort. Conclusion: These results confirm the importance of the COMTp.Val158Met genotype on tasks assessing attention and cognitive flexibility in midlife but not in healthy aging and the development of MCI. Our findings suggest that the influence of COMT changes as a function of age, decreasing from midlife to aging.

Attitude toward own aging as a risk factor for cognitive disorder in old age: 12-year evidence from the ILSE study.

Previous research has demonstrated the harmful impact of subjective aging processes (e.g., negative age self-stereotyping) on normal cognitive aging in different domains of cognitive functioning, such as memory, executive function, and fluid abilities. Recently, subjective aging has also been linked to important biomarkers of Alzheimer’s disease (AD) and dementia-related outcomes, indicating associations with pathological cognitive aging. With data from the Interdisciplinary Longitudinal Study of Adult Development and Aging (ILSE), the present study extends this research by examining the long-term effect of attitude toward own aging (ATOA) on expert-based clinical diagnosis of mild cognitive impairment (MCI) and AD in old age. In the study, 260 initially cognitively healthy participants with a mean age of 62.5 years were followed for 12 years. In the course of the study, 103 participants developed MCI and 14 received diagnosis of AD. Logistic regression models showed that baseline ATOA predicted future clinical diagnoses of MCI and AD 12 years later, while controlling for sociodemographic, genetic, and health variables. Although theoretically suggested, evidence for a mediating role of leisure-activity level and control beliefs was scarce. Our findings add to the emerging literature supporting negative views of aging as a risk factor for cognitive disorder in old age.