The Potential Role of Gustatory Function as an Early Diagnostic Marker for the Risk of Alzheimer's Disease in Subjective Cognitive Decline.

Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit. Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD. Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration. Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients. Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition.

Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage.

Introduction: Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks. Methods: We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling. Results: The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity. Discussion: Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation.

Age-related cognitive effects of the COVID-19 pandemic restrictions and associated mental health changes in Germans.

Restrictive means to reduce the spread of the COVID-19 pandemic have not only imposed broad challenges on mental health but might also affect cognitive health. Here we asked how restriction-related changes influence cognitive performance and how age, perceived loneliness, depressiveness and affectedness by restrictions contribute to these effects. 51 Germans completed three assessments of an online based study during the first lockdown in Germany (April 2020), a month later, and during the beginning of the second lockdown (November 2020). Participants completed nine online cognitive tasks of the MyBrainTraining and online questionnaires about their perceived strain and impact on lifestyle factors by the situation (affectedness), perceived loneliness, depressiveness as well as subjective cognitive performance. The results suggested a possible negative impact of depressiveness and affectedness on objective cognitive performance within the course of the lockdown. The younger the participants, the more pronounced these effects were. Loneliness and depressiveness moreover contributed to a worse evaluation of subjective cognition. In addition, especially younger individuals reported increased distress. As important educational and social input has partly been scarce during this pandemic and mental health problems have increased, future research should also assess cognitive long-term consequences.

Structural and functional brain alterations in patients with myasthenia gravis.

Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 ± 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 ± 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail.

Making the rich richer: Frontoparietal tDCS enhances transfer effects of a single-session distractor inhibition training on working memory in high capacity individuals but reduces them in low capacity individuals.

Working memory (WM) performance depends on the ability to extract relevant while inhibiting irrelevant information from entering the WM storage. This distractor inhibition ability can be trained and is known to induce transfer effects on WM performance. Here we asked whether transfer on WM can be boosted by transcranial direct current stimulation (tDCS) during a single-session distractor inhibition training. As WM performance is ascribed to the frontoparietal network, in which prefrontal areas are associated with inhibiting distractors and posterior parietal areas with storing information, we placed the anode over the prefrontal and the cathode over the posterior parietal cortex during a single-session distractor inhibition training. This network-oriented stimulation protocol should enhance inhibition processes by shifting the neural activity from posterior to prefrontal regions. WM improved after a single-session distractor inhibition training under verum stimulation but only in subjects with a high WM capacity. In subjects with a low WM capacity, verum tDCS reduced the transfer effects on WM. We assume tDCS to strengthen the frontostriatal pathway in individuals with a high WM capacity leading to efficient inhibition of distractors. In contrast, the cathodal stimulation of the posterior parietal cortex might have hindered usual compensational mechanism in low capacity subjects, i.e. maintaining also irrelevant information in memory. Our results thus stress the need to adjust tDCS protocols to well-founded knowledge about neural networks and individual cognitive differences.

Structural MRI of the basal forebrain as predictor of cognitive response to galantamine in healthy older adults-A randomized controlled double-blinded crossover study.

INTRODUCTION: Cholinesterase inhibitors can enhance cognitive functions in healthy elderly and delay cognitive decline in patients with Alzheimer`s disease (AD). However, not everyone benefits from this treatment (non-responders). Current studies show clinical meaningful improvements only in one third of AD patients treated with cholinesterase inhibitors. METHODS: Here we investigate structural magnetic resonance imaging of the basal forebrain cholinergic system volume (BFvol) as a potential predictor of cognitive response to a single dose of galantamine in healthy adults (n = 18; 59 to 75 years). RESULTS: We observed that the cognitive response to galantamine, more specifically the attention-dependent filtering performance in a delayed match-to-sample working memory task, correlated with BFvol: Only participants with high BFvol showed a significant positive effect of galantamine on the ability to filter out distracting information during the working memory encoding process. DISCUSSION: Future studies need to assess whether BFvol may serve as a predictor of the galantamine response in AD patients, too.

Psychological consequences of COVID-19 home confinement: The ECLB-COVID19 multicenter study.

BACKGROUND: Public health recommendations and government measures during the COVID-19 pandemic have enforced restrictions on daily-living. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on mental health and emotional wellbeing is undefined. Therefore, an international online survey (ECLB-COVID19) was launched on April 6, 2020 in seven languages to elucidate the impact of COVID-19 restrictions on mental health and emotional wellbeing. METHODS: The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online-survey-platform and was promoted by thirty-five research organizations from Europe, North-Africa, Western-Asia and the Americas. All participants were asked for their mental wellbeing (SWEMWS) and depressive symptoms (SMFQ) with regard to "during" and "before" home confinement. RESULTS: Analysis was conducted on the first 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%). The COVID-19 home confinement had a negative effect on both mental-wellbeing and on mood and feelings. Specifically, a significant decrease (p < .001 and Δ% = 9.4%) in total score of the SWEMWS questionnaire was noted. More individuals (+12.89%) reported a low mental wellbeing "during" compared to "before" home confinement. Furthermore, results from the mood and feelings questionnaire showed a significant increase by 44.9% (p < .001) in SMFQ total score with more people (+10%) showing depressive symptoms "during" compared to "before" home confinement. CONCLUSION: The ECLB-COVID19 survey revealed an increased psychosocial strain triggered by the home confinement. To mitigate this high risk of mental disorders and to foster an Active and Healthy Confinement Lifestyle (AHCL), a crisis-oriented interdisciplinary intervention is urgently needed.

High Working Memory Capacity at the Cost of Precision?

Working memory capacity (WMC) varies tremendously among individuals. Here, we investigate the possibility that subjects with high WMC use this limited resource more efficiently by reducing the precision with which they store information in demanding tasks. Task difficulty was increased by (a) presenting more objects to be memorized, (b) informing subjects only after the encoding phase about the relevant objects, and (c) delivering distracting features at retrieval. Precision was assessed by means of a continuous delayed-estimation task, in which object features had to be estimated from memory. High WMC subjects did not show a stronger drop in precision in difficult tasks. Instead, a positive correlation between precision and general WMC emerged. These findings suggest that high WMC subjects do not necessarily trade in quantity for quality when forming working memory (WM) representations under increasing demand. Instead, they seem to be able to devote more cognitive resources to support WM storage.

Decision-Making Deficits in Elderly Can Be Alleviated by Attention Training.

Decision-making is an important everyday function that deteriorates during normal aging. Here, we asked whether value-based decision-making can be improved in the elderly by cognitive training. We compared the effects of two training regimens on the performance in the Iowa Gambling Task (IGT), a real-life decision-making simulation task. Elderly participants (age 62-75 years) were randomized into three matched groups. The filter training (FT) group performed a selective attention task and the memory training (MT) group performed a memory storage task on five consecutive days. The control group (CG) did not perform another task besides the IGT. Only the FT group showed an improvement in IGT performance over the five days-the overall gain rose and the prominent deck B phenomenon decreased. The latter refers to the selection of cards associated with high gains and rare losses, which are nevertheless a disadvantageous choice as the frequent losses lead to a negative net outcome. As the deck B phenomenon has been associated with impaired cognitive abilities in aging, the positive effect of FT here is of special importance. In sum, attention training seems superior in improving decision-making in the elderly.

Inter-Individual Differences in Cognitive Response to a Single Bout of Physical Exercise-A Randomized Controlled Cross-Over Study.

Recent reviews have shown that acute exercise can improve cognitive functions, especially executive functions. However, a closer look at the included studies revealed a wide inter-individual variability in the effects of exercise on cognition. Therefore, thirty-nine healthy adults (age: 19-30 years) were analyzed in a randomized, controlled cross-over study with two exercise groups (n = 13 each) and a sedentary control group (n = 13). The exercise conditions included moderate (30 min at 40-59% VO2max) and high intensity interval (five × 2 min at 90% VO2max with 3 min active recovery at 40% VO2max) treadmill exercise. The main outcome assessed was cognitive performance (attention, inhibitory control, cognitive flexibility) and underlying inter-individual variability in young adults. On the group level no significant group or group × time interaction effects were observed. Using a median split, we found significant differences between low and high cognitive performers regarding cognitive function following moderate and high intensity interval treadmill exercise. Furthermore, using a pre-determined threshold we could identify responders and non-responders to acute exercise. Therefore, future research should consider individual performance requirements.

Investigating the Potential Role of Ecological Validity on Change-Detection Memory Tasks and Distractor Processing in Younger and Older Adults.

Cognitive performance is often found to be lower in older adults, especially when the task requires memory, executive functions, or selective attention. But this alleged deterioration may have been overestimated in the past due to ecologically invalid testing. To verify this possible misjudgment here we compared age-related memory performance in a typical, abstract computer task to a paper-pencil test with a real-world map and to an even more realistic task that took place in a real room with everyday objects. Retention and response intervals differed between the tasks as they had to be adjusted to the different settings. Twenty-seven younger (19-29 years old) and twenty-three older participants (61-77 years old) took part in the study. As expected younger participants outperformed the older ones in the computer task. However, although older adults' performance was better in both more realistic tasks, the delta to the young remained the same as in the computer task. Hence, these results do not support the general notion that older adults would profit from more realistic test scenarios. On the other hand, performance in a clinical screening task correlated only with the performance in the real world task suggesting that this task reflected the general cognitive status of participants better than the more abstract tasks. Finally, it was observed that the presence of task-irrelevant distractor items actually helped older adults to improve their performance in the paper pencil task arguing against the assumption of a general age-related impairment of inhibition. In sum, the present results show that age-related changes in memory are neither simply explained by reduced abilities to deal with abstract computer tasks nor by disturbed inhibition processes.

Dancing or Fitness Sport? The Effects of Two Training Programs on Hippocampal Plasticity and Balance Abilities in Healthy Seniors.

Age-related degenerations in brain structure are associated with balance disturbances and cognitive impairment. However, neuroplasticity is known to be preserved throughout lifespan and physical training studies with seniors could reveal volume increases in the hippocampus (HC), a region crucial for memory consolidation, learning and navigation in space, which were related to improvements in aerobic fitness. Moreover, a positive correlation between left HC volume and balance performance was observed. Dancing seems a promising intervention for both improving balance and brain structure in the elderly. It combines aerobic fitness, sensorimotor skills and cognitive demands while at the same time the risk of injuries is low. Hence, the present investigation compared the effects of an 18-month dancing intervention and traditional health fitness training on volumes of hippocampal subfields and balance abilities. Before and after intervention, balance was evaluated using the Sensory Organization Test and HC volumes were derived from magnetic resonance images (3T, MP-RAGE). Fourteen members of the dance (67.21 ± 3.78 years, seven females), and 12 members of the fitness group (68.67 ± 2.57 years, five females) completed the whole study. Both groups revealed hippocampal volume increases mainly in the left HC (CA1, CA2, subiculum). The dancers showed additional increases in the left dentate gyrus and the right subiculum. Moreover, only the dancers achieved a significant increase in the balance composite score. Hence, dancing constitutes a promising candidate in counteracting the age-related decline in physical and mental abilities.

Attentional Filter Training but Not Memory Training Improves Decision-Making.

Decision-making has a high practical relevance for daily performance. Its relation to other cognitive abilities such as executive control and memory is not fully understood. Here we asked whether training of either attentional filtering or memory storage would influence decision-making as indexed by repetitive assessments of the Iowa Gambling Task (IGT). The IGT was developed to assess and simulate real-life decision-making (Bechara et al., 2005). In this task, participants gain or lose money by developing advantageous or disadvantageous decision strategies. On five consecutive days we trained 29 healthy young adults (20-30 years) either in working memory (WM) storage or attentional filtering and measured their IGT scores after each training session. During memory training (MT) subjects performed a computerized delayed match-to-sample task where two displays of bars were presented in succession. During filter training (FT) participants had to indicate whether two simultaneously presented displays of bars matched or not. Whereas in MT the relevant target stimuli stood alone, in FT the targets were embedded within irrelevant distractors (bars in a different color). All subjects within each group improved their performance in the trained cognitive task. For the IGT, we observed an increase over time in the amount of money gained in the FT group only. Decision-making seems to be influenced more by training to filter out irrelevant distractors than by training to store items in WM. Selective attention could be responsible for the previously noted relationship between IGT performance and WM and is therefore more important for enhancing efficiency in decision-making.

Evolution of Neuroplasticity in Response to Physical Activity in Old Age: The Case for Dancing.

From animal research, it is known that combining physical activity with sensory enrichment has stronger and longer-lasting effects on the brain than either treatment alone. For humans dancing has been suggested to be analogous to such combined training. Here we assessed whether a newly designed dance training program that stresses the constant learning of new movement patterns is superior in terms of neuroplasticity to conventional fitness activities with repetitive exercises and whether extending the training duration has additional benefits. Twenty-two healthy seniors (63-80 years) who had been randomly assigned to either a dance or a sport group completed the entire 18-month study. MRI, BDNF and neuropsychological tests were performed at baseline and after 6 and 18 months of intervention. After 6 months, we found a significant increase in gray matter volume in the left precentral gyrus in the dancers compared to controls. This neuroplasticity effect may have been mediated by the increased BDNF plasma levels observed in the dancers. Regarding cognitive measures, both groups showed significant improvements in attention after 6 months and in verbal memory after 18 months. In addition, volume increases in the parahippocampal region were observed in the dancers after 18 months. The results of our study suggest that participating in a long-term dance program that requires constant cognitive and motor learning is superior to engaging in repetitive physical exercises in inducing neuroplasticity in the brains of seniors. Therefore, dance is highly promising in its potential to counteract age-related gray matter decline.

[Preventive strategies for dementia]. / Präventionsstrategien gegen Demenz.

In the context of the demographically induced increase in the prevalence of dementia and the simultaneous lack of causal pharmacological therapies, preventive approaches are gaining in importance. By reducing risk factors and with measures which induce neuroplasticity successful aging can be supported. This article summarizes the current developments in preventing dementia by modification of life style factors. The main focus lies on the impact of cognitive and physical activity on neuroprotection. A promising approach combines both activities within a dance training program. Further studies that meet the demanding criteria of a randomized clinical trial are urgently needed.

Optimal Cut-Off Value for Locus Coeruleus-to-Pons Intensity Ratio as Clinical Biomarker for Alzheimer's Disease: A Pilot Study.

BACKGROUND: Studies using neuromelanin-sensitive-MRI have established the locus coeruleus (LC)-to-pons intensity ratio as a biomarker for diagnosis of Parkinson's and Alzheimer's diseases. More detailed analysis is needed for exploiting the highest clinical potential of this technique. OBJECTIVE: The aim is to determine the location of the highest LC-to-pons ratio within the LC and develop an easy-to-use tool for clinical application. METHODS: Ten patients diagnosed with various stages of Alzheimer's disease (74.1±3.9 years, range 68-80, 7 females) and ten healthy elderly subjects (72.4±3.1 years, range 68-77, 5 females) participated in the study. Five subsequent slices with a thickness of 2.5 millimeters were analyzed using the image analysis tool FSL, starting with the first slice below inferior colliculus. The outcome variable was the intensity ratio between maximum values of LC and adjacent pontine region. RESULTS: The section located 10 millimeters below the inferior colliculus has the highest potential in differentiating between healthy controls and patients, with the intensity-ratio difference between groups of 12.3% and effect size of 1.577. For the cut-off value of 1.09, the sensitivity and specificity values were 100% and 80%, respectively. CONCLUSION: We consider the method a promising clinical tool to aid AD diagnosis workup.

Training of Attentional Filtering, but Not of Memory Storage, Enhances Working Memory Efficiency by Strengthening the Neuronal Gatekeeper Network.

Memory training (MT) in older adults with memory deficits often leads to frustration and, therefore, is usually not recommended. Here, we pursued an alternative approach and looked for transfer effects of 1-week attentional filter training (FT) on working memory performance and its neuronal correlates in young healthy humans. The FT effects were compared with pure MT, which lacked the necessity to filter out irrelevant information. Before and after training, all participants performed an fMRI experiment that included a combined task in which stimuli had to be both filtered based on color and stored in memory. We found that training induced processing changes by biasing either filtering or storage. FT induced larger transfer effects on the untrained cognitive function than MT. FT increased neuronal activity in frontal parts of the neuronal gatekeeper network, which is proposed to hinder irrelevant information from being unnecessarily stored in memory. MT decreased neuronal activity in the BG part of the gatekeeper network but enhanced activity in the parietal storage node. We take these findings as evidence that FT renders working memory more efficient by strengthening the BG-prefrontal gatekeeper network. MT, on the other hand, simply stimulates storage of any kind of information. These findings illustrate a tight connection between working memory and attention, and they may open up new avenues for ameliorating memory deficits in patients with cognitive impairments.

Errorless and errorful learning modulated by transcranial direct current stimulation.

BACKGROUND: Errorless learning is advantageous over trial and error learning (errorful learning) as errors are avoided during learning resulting in increased memory performance. Errorful learning challenges the executive control system of memory processes as the erroneous items compete with the correct items during retrieval. The left dorsolateral prefrontal cortex (DLPFC) is a core region involved in this executive control system. Transcranial direct current stimulation (tDCS) can modify the excitability of underlying brain functioning. RESULTS: In a single blinded tDCS study one group of young healthy participants received anodal and another group cathodal tDCS of the left DLPFC each compared to sham stimulation. Participants had to learn words in an errorless and an errorful manner using a word stem completion paradigm. The results showed that errorless compared to errorful learning had a profound effect on the memory performance in terms of quality. Anodal stimulation of the left DLPFC did not modulate the memory performance following errorless or errorful learning. By contrast, cathodal stimulation hampered memory performance after errorful learning compared to sham, whereas there was no modulation after errorless learning. CONCLUSIONS: Concluding, the study further supports the advantages of errorless learning over errorful learning. Moreover, cathodal stimulation of the left DLPFC hampered memory performance following the conflict-inducing errorful learning as compared to no modulation after errorless learning emphasizing the importance of the left DLPFC in executive control of memory.