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.

Differences in Cognitive Functioning in Two Birth Cohorts Born 20 Years Apart: Data from the Interdisciplinary Longitudinal Study of Ageing.

We compared neuropsychological functioning and prevalence of mild cognitive impairment (MCI) in two birth cohorts born 20 years apart when participants had reached the same age, i.e., the mid-60s. The study followed up 500 volunteers born 1930-1932 (C30) and 502 born 1950-1952 (C50). Participants underwent medical, neuropsychological, and psychiatric examinations in 1993-1996 (T1), 1997-2000 (T2), 2005-2008 (T3), and 2014-2016 (T4), including assessment of abstract thinking, memory performance, verbal fluency, visuo-spatial thinking, psychomotor speed, and attention. Healthy participants from C30 at T2 (n = 298) and from C50 at T4 (n = 205) were compared using multivariate ANCOVAs. Groups slightly differed with respect to age (C50: 63.86 ± 1.14 vs. C30: 66.80 ± 0.91; p < 0.05) and years of education (13.28 ± 2.89 vs. 14.56 ± 2.45). After correcting for age, C50 significantly outperformed C30 in all domains except concentration and verbal fluency. After additionally adjusting for education, C50 significantly outperformed C30 in declarative memory performances and abstract thinking only. Prevalence rates of MCI were 25.2% in C30 and 9.6% in C50 (p < 0.001). Our findings confirm the association between better educational attainment and enhanced cognitive performance in "younger" old individuals. While this association corresponds to the Flynn effect, various life course influences may have also contributed to better performance, including improvements in healthcare provision, medication, and lifestyle factors. Their overall effects may foster cognitive reserve and thus translate into the decline in MCI prevalence reported here.

Autobiographical Memory in Healthy Aging: a Decade-long Longitudinal Study.

Autobiographic memory (AM) - which is generally considered to be the most advanced human memory system - is subject to a myriad of psychological and neurobiological factors. We, therefore, examined AM longitudinally during the transition from midlife to young-old age and from young-old to old age in two birth cohorts (born 1930-1932 and 1950-1952) hence starting at age 55.14 ± 0.94 vs. 73.85 ± 0.96, respectively. Participants (n = 239) of the Interdisciplinary Longitudinal Study on Adult Development and Aging were recruited of whom 166 could be reexamined after 9 ± 0.9 years. AM was investigated for three periods of life using an established semi-structured interview; potential cognitive decline was assessed on a broad test battery. All subjects stayed cognitively healthy. Analysis of variance with repeated measures revealed age-related semantization effects with a significantly lower number of specific and thereby a higher number of general AMs exclusively from young-old to old age. This effect did not coincide with cognitive decline. In the follow-up period, a significant decrease of event-related details was significantly more pronounced in the young-old than in the old cohort and details were better recalled by the young than the old cohort. At baseline, this difference was significant for the recent past only but involved all periods at follow-up. According to our findings, AM changes in healthy aging accelerate during the transition from young-old to old age and may herald other cognitive deficits. Additionally, these AM changes in cognitively healthy subjects point at an economic process of adaptation.

Neural Correlates of Autobiographical Memory: Evidence From a Positron Emission Tomography Study in Patients With Mild Cognitive Impairment and Alzheimer's Disease.

Background: Autobiographical memory (AM) changes are the hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI). In recent neuroimaging studies, AM changes have been associated with numerous cerebral sites, such as the frontal cortices, the mesial temporal lobe, or the posterior cingulum. Regional glucose uptake in these sites was investigated for underlying subdimensions using factor analysis. Subsequently, the factors were examined with respect to AM performance in a subgroup of patients. Methods: Data from 109 memory clinic referrals, who presented with MCI (n = 60), mild AD (n = 49), or were cognitively intact, were analyzed. The glucose metabolic rates determined by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in 34 cerebral sites important for AM were investigated for underlying subdimensions by calculating factor analysis with varimax rotation. Subsequently, the respective factor scores were correlated with the episodic and semantic AM performance of 22 patients, which was measured with a semi-structured interview assessing episodic memories (characterized by event-related emotional, sensory, contextual, and spatial-temporal details) and personal semantic knowledge from three periods of life (primary school, early adulthood, and recent years). Results: Factor analysis identified seven factors explaining 69% of the variance. While patients with MCI and AD showed lower values than controls on the factors frontal cortex, mesial temporal substructures, and occipital cortex, patients with MCI presented with increased values on the factors posterior cingulum and left temporo-prefrontal areas. The factors anterior cingulum and right temporal cortex showed only minor, non-significant group differences. Solely, the factor mesial temporal substructures was significantly correlated with both episodic memories (r = 0.424, p < 0.05) and personal semantic knowledge (r = 0.547, p < 0.01) in patients with MCI/AD. Conclusions: The factor structure identified corresponds by large to the morphological and functional interrelations of the respective sites. While reduced glucose uptake on the factors frontal cortex, mesial temporal substructures, and occipital cortex in the patient group may correspond to neurodegenerative changes, increased values on the factors posterior cingulum and left temporo-prefrontal areas in MCI may result from compensatory efforts. Interestingly, changes of the mesial temporal substructures were correlated with both semantic and episodic AM. Our findings suggest that AM deficits do not only reflect neurodegenerative changes but also refer to compensatory mechanisms as they involve both quantitative losses of specific memories and qualitative changes with a semantization of memories.

Economization of cerebral activation under training: The inverse U- shaped function revisited.

As already observed as early as 1967 by Ingvar and Risberg in their pioneering work, effects of practice of working memory on cerebral functions have been confirmed repeatedly in a number of neuroimaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Accordingly, initial performance gains are typically accompanied by increased cerebral activation, while consolidation of such performance gains goes along with a subsequent decrease in activation resembling an inverse U-shaped function. This observed pattern can be interpreted as an economization of cerebral functioning as tasks are being accomplished with relatively lower effort and may also apply to other cognitive domains. However, the economization of cerebral activation under training may depend on task difficulty and training characteristics on the one hand and individual factors, including age, intelligence, cognitive reserve, education, physical and mental health on the other. These findings bear important implications for the design of neuroimaging studies and stimulation protocols, in which similar tasks are routinely repeated.

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. (PsycINFO Database Record

Elderly migrants in outpatient and inpatient care services in Baden-Württemberg/Germany.

OBJECTIVE: Given the expected underrepresentation of elderly migrant populations in healthcare utilization we examined their proportion in nursing homes and care services for the elderly. We expected that cultural aspects were rarely addressed in the services´ concepts. METHODS: A questionnaire was administered to all care providers; 66.3% of 2724 in- and outpatient services in Baden-Württemberg, Germany participated. RESULTS: 78% of the services provided healthcare to migrants, who accounted for 14.1% of the clientele. This proportion was higher in urban (e.g. Heilbronn: 16.1%) than in rural areas (e.g. Lake Constance: 7.7%) and was significantly (r = 0.545, p < .05) correlated with the proportion of migrants in the general population. 39.1% of the migrants came from Russia, Poland and Turkey. Migrants from Turkey preferred outpatients´ rather than inpatients´ services. While 87.4% of services employed migrants, only 20% of services provided measures to increase intercultural competency to their employees. CONCLUSIONS: Migrants utilize inpatient and outpatient services regularly as their proportion was closely associated to that of the general population. Although their number will likely increase in the near future, the vast majority of nursing facilities did not provide specialized measures to better meet the demands of residents with a migration background.

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.

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 [(18)F]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.

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 Alzheimer's 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.

The Positivity Effect on the Intensity of Experienced Emotion and Memory Performance in Mild Cognitive Impairment and Dementia.

AIMS: We examined the 'positivity effect' on memory performance in mild cognitive impairment (MCI) and dementia patients. METHODS: In 109 subjects (28 controls, 32 with MCI, 27 with mild and 32 with moderate dementia), we investigated free recalls (immediate and delayed) and recognition of 12 pictures. Moreover, the emotional valence of the pictures perceived and the emotions evoked in the subjects were evaluated. RESULTS: Patients with mild and moderate dementia recalled fewer pictures than those with MCI or the healthy controls. Across the groups, the positive pictures were better memorized and induced a higher arousal than the negative or neutral ones. CONCLUSIONS: Our findings indicate a positivity effect on memory performance and intensity of experience not only in healthy elderly patients but also in those with MCI or mild and moderate dementia. This effect does not refer to the compliance of the patients investigated since they perceived and experienced the pictures in the expected way.

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 Alzheimer's 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.

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.

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.