Kolassa, Iris-Tatjana
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No Evidence That Cognitive and Physical Activities Are Related to Changes in EEG Markers of Cognition in Older Adults at Risk of Dementia
An active lifestyle as well as cognitive and physical training (PT) may benefit cognition by increasing cognitive reserve, but the underlying neurobiological mechanisms of this reserve capacity are not well understood. To investigate these mechanisms of cognitive reserve, we focused on electrophysiological correlates of cognitive performance, namely on an event-related measure of auditory memory and on a measure of global coherence. Both measures have shown to be sensitive markers for cognition and might therefore be suitable to investigate potential training- and lifestyle-related changes. Here, we report on the results of an electrophysiological sub-study that correspond to previously published behavioral findings. Altogether, 65 older adults with subjective or objective cognitive impairment and aged 60-88 years were assigned to a 10-week cognitive (n = 19) or a 10-week PT (n = 21) or to a passive control group (n = 25). In addition, self-reported lifestyle was assessed at baseline. We did not find an effect of both training groups on electroencephalography (EEG) measures of auditory memory decay or global coherence (ps ≥ 0.29) and a more active lifestyle was not associated with improved global coherence (p = 0.38). Results suggest that a 10-week unimodal cognitive or PT and an active lifestyle in older adults at risk for dementia are not strongly related to improvements in electrophysiological correlates of cognition.
No Evidence That Short-Term Cognitive or Physical Training Programs or Lifestyles Are Related to Changes in White Matter Integrity in Older Adults at Risk of Dementia
Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer's disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n = 13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n = 14), or a control group (n = 20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer's disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (β ≥ 0.40, p ≤ 0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were related to FA scores at baseline (cognitive training skills and FA composite score, rs = 0.68, p = 0.05; functional physical fitness and fornix FA, r = 0.35, p = 0.03). Overall, we found no evidence of a link between short-term physical or cognitive activities and WMI changes, despite activity-related cognitive changes in older adults at risk of dementia. However, we found positive associations between the two targeted training outcomes and WMI, hinting at a potential of long-term activities to affect WMI.
Increased Levels of Antigen-Bound beta-Amyloid Autoantibodies in Serum and Cerebrospinal Fluid of Alzheimer's Disease Patients
Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
Antigen-Bound and Free β-Amyloid Autoantibodies in Serum of Healthy Adults
Physiological β-amyloid autoantibodies (Aβ-autoantibodies) are currently investigated as potential diagnostic and therapeutic tools for Alzheimer’s disease (AD). In previous studies, their determination in serum and cerebrospinal fluid (CSF) using indirect ELISA has provided controversial results, which may be due to the presence of preformed Aβ antigen-antibody immune complexes. Based on the epitope specificity of the Aβ-autoantibodies, recently elucidated in our laboratory, we developed (a) a sandwich ELISA for the determination of circulating Aβ-IgG immune complexes and (b) an indirect ELISA for the determination of free Aβ-autoantibodies. This methodology was applied to the analysis of serum samples from healthy individuals within the age range of 18 to 89 years. Neuropsychological examination of the participants in this study indicated non-pathological, age-related cognitive decline, revealed especially by tests of visual memory and executive function, as well as speed-related tasks. The ELISA serum determinations showed significantly higher levels of Aβ-IgG immune complexes compared to free Aβ-autoantibodies, while no correlation with age or cognitive performance of the participants was found.
Global EEG coherence as a marker for cognition in older adults at risk for dementia
Quantitative electroencephalography (EEG) provides useful information about neurophysiological health of the aging brain. Current studies investigating EEG coherence and power for specific brain areas and frequency bands have yielded inconsistent results. This study assessed EEG coherence and power indices at rest measured over the whole skull and for a wide frequency range as global EEG markers for cognition in a sample at risk for dementia. Since global markers are more reliable and less error‐prone than region‐ and frequency‐specific indices they might help to overcome previous inconsistencies. Global EEG coherence (1–30 Hz) and an EEG slowing score were assessed. The EEG slowing score was calculated by low‐frequency power (1–8 Hz) divided by high‐frequency power (9–30 Hz). In addition, the prognostic value of the two EEG indices for cognition and cognitive decline was assessed in a 5‐year follow‐up pilot study. Baseline global coherence correlated positively with cognition at baseline, but not with cognitive decline or with cognition at the 5‐year follow‐up. The EEG slowing ratio showed no significant association, neither with cognition at baseline or follow‐up, nor with cognitive decline over a period of 5 years. The results indicate that the resting state global EEG coherence might be a useful and easy to assess electrophysiological correlate for neurocognitive health in older adults at risk for dementia. Because of the small statistical power for the follow‐up analyses, the prognostic value of global coherence could not be determined in the present study. Future studies should assess its prognostic value with larger sample sizes.
Cognitive change is more positively associated with an active lifestyle than with training interventions in older adults at risk of dementia : a controlled interventional clinical trial
While observational studies show that an active lifestyle including cognitive, physical, and social activities is associated with a reduced risk of cognitive decline and dementia, experimental evidence from corresponding training interventions is more inconsistent with less pronounced effects. The aim of this study was to evaluate and compare training- and lifestyle-related changes in cognition. This is the first study investigating these associations within the same time period and sample.
Effects of Aging and Mild Cognitive Impairment on Electrophysiological Correlates of Performance Monitoring
Performance monitoring tasks are suitable for investigating aging-related decline in executive functions. However, little is known about performance monitoring in premature pathological aging and mild cognitive impairment (MCI). This study recorded the error-related negativity (ERN) and the correct-related negativity (CRN) as indices of performance monitoring and
compared these responses in older adults with MCI to the ones of younger and older adult controls. No differences in either ERN or CRN were found between younger and older adult controls. Compared to both control groups, we observed a more negatively pronouncedCRNin MCI subjects. Only in this group did the amplitude of theCRNnot differ from the one of the ERN. In general, larger differences between both components (i.e., ERN > CRN) were associated with better performances in cognitive tests requiring inhibition and executive control. These results indicate that electrophysiological correlates of performance monitoring (ERN and CRN) are differentially affected by aging and MCI.
Auditory Memory Decay as Reflected by a New Mismatch Negativity Score Is Associated with Episodic Memory in Older Adults at Risk of Dementia
The auditory mismatch negativity (MMN) is an event-related potential (ERP) peaking about 100-250 ms after the onset of a deviant tone in a sequence of identical (standard) tones. Depending on the interstimulus interval (ISI) between standard and deviant tones, the MMN is suitable to investigate the pre-attentive auditory discrimination ability (short ISIs, ≤ 2 s) as well as the pre-attentive auditory memory trace (long ISIs, >2 s). However, current results regarding the MMN as an index for mild cognitive impairment (MCI) and dementia are mixed, especially after short ISIs: while the majority of studies report positive associations between the MMN and cognition, others fail to find such relationships. To elucidate these so far inconsistent results, we investigated the validity of the MMN as an index for cognitive impairment exploring the associations between different MMN indices and cognitive performance, more specifically with episodic memory performance which is among the most affected cognitive domains in the course of Alzheimer's dementia (AD), at baseline and at a 5-year-follow-up. We assessed the amplitude of the MMN for short ISI (stimulus onset asynchrony, SOA = 0.05 s) and for long ISI (3 s) in a neuropsychologically well-characterized cohort of older adults at risk of dementia (subjective memory impairment, amnestic and non-amnestic MCI;n= 57). Furthermore, we created a novel difference score (ΔMMN), defined as the difference between MMNs to short and to long ISI, as a measure to assess the decay of the auditory memory trace, higher values indicating less decay. ΔMMN and MMN amplitude after long ISI, but not the MMN amplitude after short ISI, was associated with episodic memory at baseline (β= 0.38,p= 0.003;β= -0.27,p= 0.047, respectively). ΔMMN, but not the MMN for long ISIs, was positively associated with episodic memory performance at the 5-year-follow-up (β= 0.57,p= 0.013). The results suggest that the MMN after long ISI might be suitable as an indicator for the decline in episodic memory and indicate ΔMMN as a potential biomarker for memory impairment in older adults at risk of dementia.
Resting-state slow wave power, healthy aging and cognitive performance
Cognitive functions and spontaneous neural activity show significant changes over the life-span, but the interrelations between age, cognition and resting-state brain oscillations are not well understood. Here, we assessed performance on the Trail Making Test and resting-state magnetoencephalographic (MEG) recordings from 53 healthy adults (18–89 years old) to investigate associations between age-dependent changes in spontaneous oscillatory activity and cognitive performance. Results show that healthy aging is accompanied by a marked and linear decrease of resting-state activity in the slow frequency range (0.5–6.5 Hz). The effects of slow wave power on cognitive performance were expressed as interactions with age: For older (>54 years), but not younger participants, enhanced delta and theta power in temporal and central regions was positively associated with perceptual speed and executive functioning. Consistent with previous work, these findings substantiate further the important role of slow wave oscillations in neurocognitive function during healthy aging.
Development of large-scale functional networks over the lifespan
The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18–89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2–4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.