Biomedical subjects

Lars-Göran Nilsson

Publications and source records attributed to Lars-Göran Nilsson.

At least 19 recordsLinked to original sources

PubMed2006

Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon4 carriers.

Apolipoprotein E-epsilon4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondemented apolipoprotein E-epsilon4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-epsilon4 carriers, and hence likely progression to Alzheimer's disease.

Aged↗

PubMed2006

The Hypomania Checklist (HCL-32): its factorial structure and association to indices of impairment in German and Swedish nonclinical samples.

BACKGROUND: Bipolar disorders are often not recognized. Several instruments were developed but none primarily focused on hypomania. The Hypomania Checklist (HCL) is aimed at the identification of bipolarity in outpatients. Using a German and Swedish sample, we investigated if the factor structure in nonclinical samples is similar to the one reported for outpatient samples. Furthermore, we tested if people who probably had a lifetime history of hypomania report more depression or other signs of impairment and if current depression is associated with lifetime hypomania. METHOD: In the German study, participants completed the HCL-32 as an online questionnaire that also included questions about lifetime and current depression (n = 695), whereas the Swedish data relied on the paper-and-pencil version of the HCL-32 completed by a random sample from a representative population sample (n = 408). RESULTS: The factor structure of the HCL-32 was fairly similar in both samples and to the ones presented by Angst et al (J Affect Disord 2005;88:217-33). People reporting "highs" (> or =4 days and experiencing negative consequences) not only endorsed more HCL-32 symptoms but also had higher rates of current and former depression and psychotherapy. Level of current depression was also associated with lifetime hypomanic symptoms. DISCUSSION AND LIMITATION: An "active-elated" and "risk-taking/irritable" factor of hypomania can be distinguished with the HCL-32 in clinical and nonclinical samples. Based on our results, the HCL-32 might even be useful as screening tool in nonclinical samples and not only in depressed outpatients. However, our data do not allow estimating sensitivity and specificity of the HCL-32 because structured clinical interviews were not included.

Adolescent↗

PubMed2006

Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers.

The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Aged↗

PubMed2006

Reduced hippocampal volume in non-demented carriers of the apolipoprotein E epsilon4: relation to chronological age and recognition memory.

Apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE epsilon4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition-memory performance between AD-symptom-free carriers (N=30) and non-carriers (N=30) of the APOE epsilon4 (age range: 49-79 years). We observed reduced right hippocampal volume in APOE epsilon4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE epsilon4 carriers made significantly more false alarms in the recognition-memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

Age Factors↗

PubMed2006

Cerebral changes on MRI and cognitive function: the CASCADE study.

The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperintensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4+/-3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies.

Age Distribution↗

PubMed2006

Negative association of testosterone on spatial visualization in 35 to 80 year old men.

Androgens have been linked to visuospatial ability. We examined the relationship between serum free testosterone (T) levels and spatial visualization ability in a population-based sample of 450 healthy men between the ages of 35 and 80 years. They were tested on block design and Mini Mental State Examination (MMSE) draw-a-figure, as well as tasks assessing episodic memory, semantic memory, procedural memory, and verbal fluency. Blood was analyzed for free T and estradiol. Participants were grouped into high or low free T based on age-specific median values. Participants with low free T performed at a superior level on both the block design task and draw-a-figure task as compared to participants with high free T. The results are discussed within the scant body of research on androgens and cognition in men.

Adolescent↗

PubMed2006

How do health and biological age influence chronological age and sex differences in cognitive aging: moderating, mediating, or both?

Much research on cognitive competence in normal older adults has documented age and sex differences. The authors used new cross-sectional data from the Victoria Longitudinal Study (VLS) (n=386; age 61 to 95 years) to examine how health and biological age influence age and sex differences in cognitive aging. The authors found evidence for both moderating and mediating influences. Age differences were moderated by health status, such that the negative effects of age were most pronounced among participants of relatively better health. Sex differences were moderated by health and were more pronounced among participants reporting comparatively poorer health. Although health mediated a notable amount of age-related cognitive variation, BioAge mediated considerably more variance, even after statistical control for differences in health. A complex pattern emerged for the mediation of sex differences: Although BioAge accounted for sex-related variation in cognitive performance, health operated to suppress these differences. Overall, both health and BioAge predicted cognitive variation independently of chronological age.

Aged↗

PubMed2006

The influence of APOE status on episodic and semantic memory: data from a population-based study.

In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.

Adult↗

PubMed2006

What people believe about memory.

Two representative samples of adult Norwegians (n=2000) were asked a set of general and specific questions regarding their beliefs and opinions about human memory. The results indicate that on many questions, such as time of the earliest memories, inhibiting effects of collaboration, and memory for dramatic versus ordinary events, the views of the general public concurred with current research findings, and people in general had realistic views about their own memory performance. On other questions, such as the reliability of olfactory as compared with visual and auditory memory, the memory of small children in comparison with that of adults, the likelihood of repression of adult traumatic memories, and on more general questions such as the possibility of training memory and the capacity limitations of long-term memory, a large proportion of the participants expressed views that are less supported by scientific evidence. Implications of these findings are briefly discussed.

Adult↗

PubMed2006

Musculoskeletal pain complaints and performance on cognitive tasks over the adult life span.

The present study aimed at comparing participants with and without self reported musculoskeletal pain in a normal population with regard to performance on a range of tests for episodic memory, semantic memory, and other cognitive functions and to see if expected differences interacted with age. The results showed that participants with pain performed worse on a range of tasks as compared to participants without pain, and that these differences occurred regardless of age. The most robust effects of pain were displayed on tests for vocabulary and construction ability as these were the only effects that remained significant after controlling for years of education and reported depression in separate analyses. When depression and education were controlled for in the same analysis, even these effects were eliminated, suggesting interplay between pain, depressive status, and educational level in the negative effects on cognitive functioning.

Adult↗

PubMed2005

Structure-function correlates of cognitive decline in aging.

To explore neural correlates of cognitive decline in aging, we used longitudinal behavioral data to identify two groups of older adults (n = 40) that differed with regard to whether their performance on tests of episodic memory remained stable or declined over a decade. Analysis of structural and diffusion tensor imaging (DTI) revealed a heterogeneous set of differences associated with cognitive decline. Manual tracing of hippocampal volume showed significant reduction in those older adults with a declining memory performance as did DTI-measured fractional anisotropy in the anterior corpus callosum. Functional magnetic resonance imaging during incidental episodic encoding revealed increased activation in left prefrontal cortex for both groups and additional right prefrontal activation for the elderly subjects with the greatest decline in memory performance. Moreover, mean DTI measures in the anterior corpus callosum correlated negatively with activation in right prefrontal cortex. These results demonstrate that cognitive decline is associated with differences in the structure as well as function of the aging brain, and suggest that increased activation is either caused by structural disruption or is a compensatory response to such disruption.

Adaptation, Physiological↗

PubMed2005

Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.

BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.

Adult↗

PubMed2005

Stability, growth, and decline in adult life span development of declarative memory: cross-sectional and longitudinal data from a population-based study.

Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (N=967) was assessed to control for practice effects. For episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.

Adult↗

PubMed2005

Studying individual aging in an interindividual context: typical paths of age-related, dementia-related, and mortality-related cognitive development in old age.

This study has 2 objectives: (a) to explore typical paths of cognitive development associated with aging, terminal decline, and dementia and (b) to promote and illustrate an individual-oriented approach to the study of cognitive aging based on longitudinal panel data from a population-based sample (N = 500; age range-sub(T1)= 60-80, where T refers to time) tested at 3 occasions 5 years apart. Results document interindividual differences in multivariate patterns of change. Although cognitive changes generally covary, the present study indicates that subgroups of individuals develop along different paths characterized by selective changes in subsets of cognitive functions. Typical progression of dementia followed a developmental cascade from low declarative memory, via low functioning across all observed cognitive measures, to dementia diagnosis, and finally, death.

Aged↗

PubMed2005

The novelty effect: support for the Novelty-Encoding Hypothesis.

In two experiments, we examined the "Novelty-Encoding Hypothesis" proposed by Tulving and Kroll (1995), suggesting that the encoding of online information into long-term memory is influenced by its novelty and that novelty increases recognition performance. In Phase 1 (familiarization phase), subjects participated in a standard memory experiment in which different types of materials (verbs and nouns) were studied under different encoding conditions (enactment and non-enactment) and were tested by an expected recognition test. In Phase 2 (critical phase), subjects evaluated the materials (both familiar materials which were encoded earlier in Phase 1, and novel materials which were not presented earlier in Phase 1) in a frequency judgment task and were given an unexpected recognition test. The results of both experiments showed that novel items were recognized better than familiar items. This result held true for both hit rates - false alarms and hit rates. The novelty effect was observed for different subjects (Swedish and Japanese), different materials (verbs and nouns; high frequency and low frequency), and different types of encoding in Phase 1 (enactment and non-enactment). These findings provide support for the "Novelty-Encoding Hypothesis" stating that the effect is based on the encoding of target items at the time of the critical study (Phase 2). A comparison between the present experiments and the Tulving and Kroll (1995), Dobbins, Kroll, Yonelinas & Liu (1998) and Greene (1999) studies suggests that the novelty effect is more pronounced under incidental encoding than under intentional encoding.

Analysis of Variance↗

PubMed2005

Treatment of chronic stress in employees: subjective, cognitive and neural correlates.

This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N=27) and control (N=23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

Adaptation, Psychological↗

PubMed2005

Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults.

The catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val158Met polymorphism in the COMT gene on individual differences and changes in cognition (executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions (verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial (block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele (with higher enzyme activity) compared with carriers of the Met/Met genotype (with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.

Adult↗

PubMed2004

The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study.

Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account.

Aged↗