The effects of a moderate physical activity intervention on physical fitness and cognition in healthy elderly with low levels of physical activity: a randomized controlled trial.

BACKGROUND: Increasing physical activity is one of the most promising and challenging interventions to delay or prevent cognitive decline and dementia. METHODS: We conducted a randomized controlled trial to assess the effects of a physical activity intervention, aimed at increasing step count, in elderly with low levels of physical activity on measures of strength, balance, aerobic capacity, and cognition. Participants were assigned to 9 months of exercise counseling or active control. RESULTS: The intention-to-treat analyses show that the intervention, compared to control, increases the level of physical activity, but has no significant effect on physical fitness and cognition. Those who increased their physical activity with 35% or more show significant improvements in aerobic capacity, gait speed, verbal memory, executive functioning, and global cognition, compared to those who did not achieve a 35% increase. LIMITATIONS: The number of participants that achieved the intended improvement was lower than expected. CONCLUSION: Responder analyses suggest an improvement of physical fitness and cognition in those who achieved an increase in physical activity of at least 35%. TRIAL REGISTRATION: The trial protocol is registered at the Dutch Trial Register NL5675, August 1, 2016.

The long-term relation between physical activity and executive function in the Rotterdam Study.

BACKGROUND: Research on the association between physical inactivity and cognitive decline and dementia is dominated by studies with short-term follow-up, that might be biased by reverse causality. OBJECTIVE: Investigate the long-term association between physical activity, cognition, and the rate of age-associated cognitive decline. METHODS: We investigated the association between late-life physical activity and executive functioning and rate of decline of executive abilities during follow-up of up to 16 years, in 3553 participants of the prospective Rotterdam Study cohort. Measurement took place in 1997-1999, 2002-2004, 2009-2011, and 2014-2015. RESULTS: At baseline (age ± 72 years), higher levels of physical activity were associated with higher levels of executive functioning (adjusted mean difference = 0.03, 95% CI: 0.00 ; 0.06, p = 0.03). This difference remained intact up to 16 years of follow-up. The level of physical activity at baseline was unrelated to the rate of decline of executive abilities over time, in the whole group (adjusted mean difference in changetime*physical activity = 0.00, 95% CI: -0.00 ; 0.01, p = 0.31). However, stratification by APOE genotype showed that the accelerated decline of executive abilities observed in those with the ApoE-ε4 allele might be attenuated by higher levels of physical activity in late adulthood (ApoE-ε4 carriers: Btime*physical activity = 0.01, 95% CI: 0.00 ; 0.01, p = 0.03). CONCLUSION: Higher levels of physical activity in late adulthood are related to higher levels of executive functioning, up to 16 years of follow-up. Accelerated decline of executive abilities observed in those with the ApoE-ε4 allele might be mitigated by higher levels of physical activity.

Food-Related Brain Activation Measured by fMRI in Adults with Prader-Willi Syndrome.

(1) Background: Prader-Willi syndrome (PWS) is characterized by hyperphagia, resulting in morbid obesity if not controlled. The primary aim of this study was to investigate whether PWS patients show altered activation of brain areas involved in hunger. As a secondary objective, we assessed whether there is an association between these brain areas and several endocrine and metabolic factors in the fasting state. (2) Methods: 12 PWS adults and 14 healthy controls (siblings) performed a food-related experimental task after an overnight fast while brain activation in regions of interest was measured by functional MRI. (3) Results: In controls, significantly more activation was found in the left insula (p = 0.004) and the bilateral fusiform gyrus (p = 0.003 and 0.013) when the individuals were watching food as compared to non-food pictures, which was absent in PWS patients. Moreover, in PWS adults watching food versus non-food pictures a significant negative correlation for glucose and right amygdala activation (p_fwe = 0.007) as well as a positive correlation for leptin and right anterior hippocampus/amygdala activation (p_fwe = 0.028) was demonstrated. No significant associations for the other hormonal and metabolic factors were found. (4) Conclusions: PWS individuals show aberrant food-related brain activation in the fasting state. Leptin is associated with activation within the neural motivation/reward circuitry, while the opposite is true for glucose.

Effects of binaural and monaural beat stimulation on attention and EEG.

Nowadays a popular technique to improve mood and cognition is auditory beat stimulation (ABS), which is thought to induce a frequency-following response of brainwaves. The main types of ABS are monaural beats (MB) and binaural beats (BB). BB involves the presentation of a specific frequency to one ear and another frequency to the other ear which may induce neural entrainment. A difference between the frequencies of 40 Hz is assumed to improve cognition. The present study examined the effect of 40 Hz binaural beats (BB) and monaural beats (MB) on attention and electroencephalography (EEG). A total of 25 first-year psychology students (11 males, 14 females) performed a Flanker task while EEG was recorded during the 5 min-presentation of pink noise (PN), MB and BB. With respect to attention, as measured by the Flanker task, the number of false responses in the BB condition was smaller than that in the PN condition while the number of false responses in the MB condition was larger as compared to the PN condition. As there was no association of BB with a consistent increase in absolute 40 or 45 Hz power compared to PN or MB, EEG recordings could not confirm the hypothesized neural entrainment in the brain. Overall, the current findings show that listening to 40 Hz BB improves attention but do not show the occurrence of neural entrainment. Future research is recommended to include a larger sample, to use a broader cognitive test battery and to present auditory beats with a longer duration.

Plasma Brain-Derived Neurotropic Factor Levels Are Associated with Aging and Smoking But Not with Future Dementia in the Rotterdam Study.

BACKGROUND: Brain-derived neurotropic factor (BDNF) plays a vital role in neuronal survival and plasticity and facilitates long-term potentiation, essential for memory. Alterations in BDNF signaling have been associated with cognitive impairment, dementia, and Alzheimer's disease. Although peripheral BDNF levels are reduced in dementia patients, it is unclear whether changes in BDNF levels precede or follow dementia onset. OBJECTIVE: In the present study, we examined the association between BDNF plasma levels and dementia risk over a follow-up period of up to 16 years. METHODS: Plasma BDNF levels were assessed in 758 participants of the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up until January 2016. Associations of plasma BDNF and incident dementia were assessed with Cox proportional hazards models, adjusted for age and sex. Associations between plasma BDNF and lifestyle and metabolic factors are investigated using linear regression. RESULTS: During a follow up of 3,286 person-years, 131 participants developed dementia, of whom 104 had Alzheimer's disease. We did not find an association between plasma BDNF and risk of dementia (adjusted hazard ratio 0.99; 95%CI 0.84-1.16). BDNF levels were positively associated with age (B = 0.003, SD = 0.001, p = 0.002), smoking (B = 0.08, SE = 0.01, p = < 0.001), and female sex (B = 0.03, SE = 0.01, p = 0.03), but not with physical activity level (B = -0.01, SE = 0.01, p = 0.06). CONCLUSION: The findings suggest that peripheral BDNF levels are not associated with an increased risk of dementia.

Impaired neuropsychological functioning in patients with hypopituitarism.

Background: Treatment of pituitary pathology mostly does not result in complete recovery of impairment in cognitive functioning. The primary aim of the current study was to assess cognitive impairment in patients with stable replacement therapy for hypopituitarism during the last 6 months prior to inclusion. It was expected that patients showed subjective and objective subnormal scores on neuropsychological functioning. Methods: Forty-two patients (40% men, 49 ± 15 years) treated for hypopituitarism conducted a neuropsychological test battery, including the Cognitive Failures Questionnaire (CFQ), 15-Word test (15-WT), Cambridge Neuropsychological Test Automated Battery (CANTAB) Motor Screening Task (MOT), Spatial Working Memory (SWM) and Affective Go/No-go (AGN). Results were compared to reference values of healthy norm groups. Results: Male and female participants scored significantly worse on the CFQ (P < .01, d = 0.91-4.09) and AGN mean correct latency (P < .01, d = 1.66 and 1.29, respectively). Female participants scored significantly worse on 15-WT direct recall (P = .01, d = 0.66), 15-WT delayed recall (P = .01, d = 0.79), SWM total errors (P = .05, d = 0.41), SWM strategy (P = .04, d = 0.43), AGN errors of commission (P = .02, d = 0.56) and omission (P = .04, d = 0.41). Conclusion: This study shows that subjective cognitive functioning is worse in patients treated for hypopituitarism compared to reference data. Also, female participants treated for hypopituitarism score worse on objective aspects of memory and executive functioning compared to reference data. Besides worse focus attention, this objective cognitive impairment was not found in male participants. It is recommended to conduct additional research, which focuses on the design and evaluation of a cognitive remediation therapy, aimed at compensation of impairments in different aspects of memory and executive functioning.

Psychological well-being and illness perceptions in patients with hypopituitarism.

OBJECTIVE: The primary aim of the current study was to objectify a spectrum of persisting subjective psychological complaints in patients with hypopituitarism, at least six months after normalizing of the hormonal disturbances. Also, gender differences on these outcomes were investigated. The secondary aim was to identify illness perceptions and causal attributions within this patient group. METHODS: A total of 42 adult participants (60% females) with treated hypopituitarism once filled out a number of psychological questionnaires. The Profile of Mood States (POMS) and the Hospital Anxiety and Depression Scale (HADS) assessed mood and the Symptom Checklist-90 (SCL-90) and the Work and Social Adjustment Scale (WSAS) assessed well-being. Illness perceptions were identified using the Illness Perceptions Questionnaire-Brief Dutch Language Version (IPQ-B DLV) and causal attributions by using the Causal Attribution List (CAL). Patient outcomes were compared to reference values of healthy norm groups. RESULTS: Participants scored significantly worse on the POMS depression, anger, fatigue and tension subscales, the SCL-90 psychoneuroticism, depression, inadequacy of thinking and acting and sleeping problems subscales and all subscales of the WSAS when compared to reference data. Women also scored worse on depression (HADS) and somatic symptoms (SCL-90). Compared to other illnesses, patients with hypopituitarism have more negative and realistic illness perceptions on consequences, timeline, identity and emotions. Participants attributed their complaints more to physical causes than psychological causes. CONCLUSION: Despite normalization of hormonal disturbances, patients with hypopituitarism in general can still experience problems during daily living, such as negative mood states and a decreased psychological well-being.

The Effects of Binaural and Monoaural Beat Stimulation on Cognitive Functioning in Subjects with Different Levels of Emotionality.

Today, binaural and monaural beats are offered over the Internet or by mental health institutes to improve wellbeing or cognitive functioning. This improvement is explained by the assumption that the brain adapts its brainwave frequency to the frequency of the auditory beat. The present study examined the effects of binaural and monaural beat stimulation on attention and working memory in high and low emotional participants. A group of 24 participants (16 females, 8 males) between 19 and 31 years old (M = 22.33, SD = 3.42) performed a Flanker task to measure attention and a Klingberg task to measure working memory while listening to white noise (WN), 40 Hz gamma binaural beat (BB) and 40 Hz gamma monaural beat (MB). Speed of performance on all three levels of difficulty of the Flanker attention task was faster under the BB and MB condition than under WN. No differences were found between BB and MB conditions. With respect to the quality of performance on the Flanker attention task and the Klingberg working memory task no significant differences under the WN, MB, and BB condition were found. Finally, as participants with low or high emotionality did not respond differently to BB and MB under any of the conditions, effects of BB and MB seem similar in high and low emotional participants. The present study supports the notion that faster attention processing may equally be attributed to the influence of BB and MB. Further research is recommended to gain more insight in the role of factors such as duration of stimulation of BB and MB, frequency range, most appropriate carrier tones, and the role of personality traits.

Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: a randomized clinical trial in adult growth hormone deficiency.

BACKGROUND: The aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment. METHODS: A randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of - 2 to - 1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires. RESULTS: Data from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor. CONCLUSIONS: The adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov , number NCT01877512.

The Effects of Physical Activity and Fitness in Adolescence on Cognition in Adulthood and the Role of Insulin-Like Growth Factor I.

BACKGROUND: Physical activity and fitness in adolescence may improve cognition in adulthood by increasing insulin-like growth factor I (IGF-I). METHODS: As part of the Amsterdam Growth and Health Longitudinal Study, following subjects from age 13 to 42 years, physical activity and fitness of 303 subjects were assessed annually between the ages 13 to 16. At mean age 36, physical activity, fitness and IGF-I were measured. At mean age 42, IGF-I and cognitive factors (ie, executive functioning and visual-spatial memory) were measured. The linear regression of physical activity and fitness in adolescence and IGF-I in adulthood on cognitive scores in adulthood was investigated. RESULTS: A significant association was found in males between physical activity in adolescence and executive function in adulthood (Spatial Working Memory Between Errors: ß = -.18, B = -.13, 95% CI = -.259 to -.010; Spatial Working Memory Strategy: ß = -.20, B = -.08, 95% CI = -.147 to -.014). No association between physical activity or fitness in adolescence and cognitive function in adulthood was found in females, nor any intermediate role for IGF-I in either sex. CONCLUSIONS: The results suggest a stimulating effect of adolescent physical activity in males on executive functions in adulthood, emphasizing the importance of an active lifestyle among adolescent males.

Cognitive functioning during long-term tamoxifen treatment in postmenopausal women with breast cancer.

OBJECTIVE: Endocrine therapy is widely used-often for many years-in women with breast cancer. Yet little is known about cognitive functioning after long-term use of tamoxifen. We examine cognitive sequelae, approximately 3 years after diagnosis, in postmenopausal women with breast cancer who were treated with adjuvant tamoxifen. METHODS: Data from participants who underwent surgical operation with or without radiotherapy, participants who received adjuvant tamoxifen, and healthy controls were collected. Neuropsychological tests were administered, and participants completed questionnaires on health-related quality of life (Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality-of-Life Questionnaire), menopausal symptoms (Functional Assessment of Cancer Therapy-Breast endocrine symptom subscale), and anxiety and depression (Hopkins Symptom Checklist). RESULTS: In total, 107 women participated (adjuvant tamoxifen group, n = 20; surgical operation/radiotherapy group, n = 43; healthy control group, n = 44). Women in the adjuvant tamoxifen group had received tamoxifen for a mean (SD) of 31.5 (18.6) months (range, 15-79 mo) and performed worse on verbal memory than the surgical operation/radiotherapy group (P < 0.05) and the healthy control group (P < 0.05). Participants in the adjuvant tamoxifen group performed worse on measures of fluency than healthy controls (P < 0.05). Furthermore, women in the adjuvant tamoxifen group reported worse cognitive functioning (P < 0.05) than women in the surgical operation/radiotherapy group or the healthy control group. CONCLUSIONS: Our results provide insights into cognitive functioning in women who receive long-term adjuvant tamoxifen treatment. By adding the surgical operation/radiotherapy group, we could control for the mental and physical influences of the diagnosis and treatment of breast cancer. Cognitive domains that rely on verbal abilities (verbal memory and fluency) seem to be at risk for deterioration after treatment with tamoxifen.

Functional connectivity and cognitive decline over 3 years in Parkinson disease.

OBJECTIVE: To evaluate fMRI whole-brain resting-state functional connectivity changes in relation to cognitive decline in Parkinson disease (PD) over a 3-year period. METHODS: Resting-state fMRI scans were acquired in 55 patients with PD (mean age 65.8 years, SD 6.37; average disease duration 9.24 years, SD 3.96) and 15 matched controls (mean age 64.4 years, SD 8.65). We first performed overall (i.e., 1 whole-brain mean) as well as regional (i.e., for all individual regions of interest) functional connectivity analyses, in which we compared subject groups cross-sectionally. After a 3-year follow-up period, 36 patients with PD and 12 controls were rescanned to study functional connectivity changes over time and correlate the changes in functional connectivity with deteriorating cognitive and motor function in the PD sample. RESULTS: In the cross-sectional analysis, we found widespread decreases of resting-state functional connectivity in patients with PD in comparison to controls. Subsequent comparison between the 2 timepoints revealed that patients with PD displayed further decreases in functional connectivity independent of aging effects. These functional connectivity changes were most prominent for posterior parts of the brain and correlated across time with clinical measures of disease progression, especially cognitive decline. CONCLUSIONS: In this fMRI study in PD, we demonstrated a progressive loss of resting-state functional connectivity over a period of 3 years for multiple brain regions, especially in posterior parts of the brain. The strong correlation with decreasing cognitive performance supports the pathophysiologic role of reduced functional connectivity in cognitive decline and the development of dementia in PD.

The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study.

Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM), paired associate learning (PAL), and IQ tests were analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease.

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

UNLABELLED: Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. TRIAL REGISTRATION: ClinicalTrials.gov NCT00626080.

Predicting dementia in Parkinson disease by combining neurophysiologic and cognitive markers.

OBJECTIVE: To assess the ability of neurophysiologic markers in conjunction with cognitive assessment to improve prediction of progression to dementia in Parkinson disease (PD). METHODS: Baseline cognitive assessments and magnetoencephalographic recordings from 63 prospectively included PD patients without dementia were analyzed in relation to PD-related dementia (PDD) conversion over a 7-year period. We computed Cox proportional hazard models to assess the risk of converting to dementia conveyed by cognitive and neurophysiologic markers in individual as well as combined risk factor analyses. RESULTS: Nineteen patients (30.2%) developed dementia. Baseline cognitive performance and neurophysiologic markers each individually predicted conversion to PDD. Of the cognitive test battery, performance on a posterior (pattern recognition memory score < median; hazard ratio (HR) 6.80; p = 0.001) and a fronto-executive (spatial span score < median; HR 4.41; p = 0.006) task most strongly predicted dementia conversion. Of the neurophysiologic markers, beta power < median was the strongest PDD predictor (HR 5.21; p = 0.004), followed by peak frequency < median (HR 3.97; p = 0.016) and theta power > median (HR 2.82; p = 0.037). In combination, baseline cognitive performance and neurophysiologic measures had even stronger predictive value, with the combination of impaired fronto-executive task performance and low beta power being associated with the highest dementia risk (both risk factors vs none: HR 27.3; p < 0.001). CONCLUSIONS: Combining neurophysiologic markers with cognitive assessment can substantially improve dementia risk profiling in PD, providing potential benefits for clinical care as well as for the future development of therapeutic strategies.

Disrupted brain network topology in Parkinson's disease: a longitudinal magnetoencephalography study.

Although alterations in resting-state functional connectivity between brain regions have previously been reported in Parkinson's disease, the spatial organization of these changes remains largely unknown. Here, we longitudinally studied brain network topology in Parkinson's disease in relation to clinical measures of disease progression, using magnetoencephalography and concepts from graph theory. We characterized whole-brain functional networks by means of a standard graph analysis approach, measuring clustering coefficient and shortest path length, as well as the construction of a minimum spanning tree, a novel approach that allows a unique and unbiased characterization of brain networks. We observed that brain networks in early stage untreated patients displayed lower local clustering with preserved path length in the delta frequency band in comparison to controls. Longitudinal analysis over a 4-year period in a larger group of patients showed a progressive decrease in local clustering in multiple frequency bands together with a decrease in path length in the alpha2 frequency band. In addition, minimum spanning tree analysis revealed a decentralized and less integrated network configuration in early stage, untreated Parkinson's disease that also progressed over time. Moreover, the longitudinal changes in network topology identified with both techniques were associated with deteriorating motor function and cognitive performance. Our results indicate that impaired local efficiency and network decentralization are very early features of Parkinson's disease that continue to progress over time, together with reductions in global efficiency. As these network changes appear to reflect clinically relevant phenomena, they hold promise as markers of disease progression.

Resting-state functional connectivity as a marker of disease progression in Parkinson's disease: A longitudinal MEG study.

The assessment of resting-state functional connectivity has become an important tool in studying brain disease mechanisms. Here we use magnetoencephalography to longitudinally evaluate functional connectivity changes in relation to clinical measures of disease progression in Parkinson's disease (PD). Using a source-space based approach with detailed anatomical mapping, functional connectivity was assessed for temporal, prefrontal and high order sensory association areas known to show neuropathological changes in early clinical disease stages. At baseline, early stage, untreated PD patients (n = 12) had lower parahippocampal and temporal delta band connectivity and higher temporal alpha1 band connectivity compared to controls. Longitudinal analyses over a 4-year period in a larger patient group (n = 43) revealed decreases in alpha1 and alpha2 band connectivity for multiple seed regions that were associated with motor or cognitive deterioration. In the earliest clinical stages of PD, delta and alpha1 band resting-state functional connectivity is altered in temporal cortical regions. With disease progression, a reversal of the initial changes in alpha1 and additional decreases in alpha2 band connectivity evolving in a more widespread cortical pattern. These changes in functional connectivity appear to reflect clinically relevant phenomena and therefore hold promise as a marker of disease progression, with potential predictive value for clinical outcome.

Cognitive decline in Parkinson's disease is associated with slowing of resting-state brain activity: a longitudinal study.

The pathophysiological mechanisms of Parkinson's disease (PD)-related dementia (PDD) are still poorly understood. Previous studies using electroencephalography (EEG) and magnetoencephalography (MEG) have demonstrated widespread slowing of oscillatory brain activity as a neurophysiological characteristic of PD-related dementia. Here, we use MEG to longitudinally study early changes in oscillatory brain activity in initially nondemented PD patients that may be associated with cognitive decline. Using a longitudinal design, resting-state MEG recordings were performed twice at an approximate 4-year interval in 14 healthy controls and 49 PD patients. Changes in peak frequency and in relative spectral power for 10 brain regions were analyzed in relation to clinical measures of cognitive and motor function. In contrast to healthy controls, PD patients showed a slowing of the dominant peak frequency. Furthermore, analysis per frequency band revealed an increase in theta power over time, along with decreases in alpha1 and alpha2 power. In PD patients, decreasing cognitive performance was associated with increases in delta and theta power, as well as decreases in alpha1, alpha2, and gamma power, whereas increasing motor impairment was associated with a theta power increase only. The present longitudinal study revealed widespread progressive slowing of oscillatory brain activity in initially nondemented PD patients, independent of aging effects. The slowing of oscillatory brain activity strongly correlated with cognitive decline and therefore holds promise as an early marker for the development of dementia in PD.

The GH/IGF-I Axis and Cognitive Changes across a 4-Year Period in Healthy Adults.

After the age of 40, the amount of growth hormone in humans decreases. The reduced activity of the GH-IGF axis may play a role in age-related cognitive impairments. In the present study, mood and cognition of 30 healthy subjects (7 males, 23 females, aged 41-76 yr, mean age 60.9 ± 9.0) were examined twice. At baseline, we determined fasting blood levels of GH and IGF-I. Mood and cognitive status were assessed at baseline and after, on the average, 3 years and 9 months of followup. Working memory performance decreased over the years in the low IGF-group (P = .007), but not the high IGF-I group. Higher levels of GH were related with a better working memory at the second test (r = 0.42, P = .01) while higher levels of IGF-I tended to be related with a better working memory (r = 0.3, P = .06). The results suggest that higher serum levels of GH and IGF-I preserve the quality of working memory functions over the years.

SPEM dysfunction and general schizotypy as measured by the SSQ: a controlled study.

BACKGROUND: SPEM dysfunction is a well-known phenomenon in schizophrenia. The principal aim of the present study was to examine whether SPEM dysfunction is already observable in subjects scoring high on a specific measure of schizotypy (SSQ General Schizotypy) that was selected because of its intimate relationship with schizophrenic prodromal unfolding. METHODS: Applying ANOVAs, we determined the relationship of subjects' scores on SSQ General Schizotypy and eye movements elicited by targets of different speed. We also examined whether there exists an association between our schizotypy measure and pupil size. RESULTS: We found more SPEM dysfunction in subjects scoring high on SSQ General Schizotypy than in subjects scoring average on that factor, irrespective of the speed of the target. No relationship was found between baseline pupil size and General Schizotypy. CONCLUSION: The present study provides additional evidence that SPEM dysfunction is associated with schizotypic features that precede the onset of schizophrenia and is already observable in general population subjects that show these features.