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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.

BackgroundWith increasing aging populations worldwide, developing interventions against age-associated cognitive decline is particularly important. Evidence suggests that combination of brain stimulation with cognitive training intervention may enhance training effects in terms of performance gain or transfer to untrained domains. This protocol describes a Phase IIb clinical trial that investigates the intervention effects of training combined with brain stimulation in older adults.MethodsThe TrainStim-Cog study is a monocentric, randomized, single-blind, placebo-controlled intervention. The study will investigate cognitive training with concurrent anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (target intervention) compared to cognitive training with sham stimulation (control intervention) over nine sessions in 3 weeks, consisting of a letter updating task, and a three-stage Markov decision-making task. Fifty-six older adults will be recruited from the general population. Baseline assessment will be performed including neuropsychological screening and performance on training tasks. Participants will be allocated to one of the two study arms using block-wise randomization stratified by age and baseline performance with a 1:1 allocation ratio. Primary outcome is performance in the letter updating task after training under anodal tDCS compared to sham stimulation. Secondary outcomes include performance changes in the decision-making task and transfer tasks, as well as brain structure and functional networks assessed by structural, and functional magnetic resonance imaging (MRI) that are acquired pre- and post-intervention.SignificanceThe main aim of the TrainStim-Cog study is to provide evidence for behavioral and neuronal effects of tDCS-accompanied cognitive training and to elucidate the underlying mechanisms in older adults. Our findings will contribute toward developing efficient interventions for age-associated cognitive decline.Trial registrationThis trial was retrospectively registered at Clinicaltrials.gov Identifier: NCT03838211 at February 12, 2019, https://clinicaltrials.gov/ct2/show/NCT03838211.Protocol versionBased on BB 004/18 version 1.2 (May 17, 2019).

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.

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. [ABSTRACT FROM AUTHOR]