Current treatment in late-life cognitive impairment and dementia is still limited, and there is no cure for brain tissue degeneration or reversal of cognitive decline. Physical activity represents a promising non-pharmacological interventional approach in many diseases causing cognitive impairment, but its effect on brain integrity is still largely unknown. Especially research of cerebral alterations in disease state that goes beyond observations of clinical improvement is crucial to understand disease processes and possible effective treatments. In this systematic review, we address the question how physical activity and fitness in mild cognitive impairment (MCI) and Alzheimer's disease (AD) influences brain architecture compared to cognitively healthy elderly. We review both interventional studies comprising aerobic, coordinative and resistance exercises and observational studies on fitness and physical activity combined with Magnetic Resonance imaging (MRI). Different MRI approaches were included such as volumetric and structural analyses, Diffusion Tensor Imaging (DTI), functional MRI and Cerebral Blood Flow (CBF). We evaluate MRI results for different exercise modalities and performed a methodological evaluation of interventional studies in cognitive decline compared to normal aging. According to our results, among 12 interventions in AD/MCI, aerobic exercise is most frequently applied (9 studies). Interventions in AD/MCI altogether reveal a higher methodological quality compared to interventions in healthy elderly (8.33 ± 2.19 vs. 6.25 ± 2.36 out of 13 points), with most frequent missing aspects related to descriptions of complications, lack of intention-to-treat and statistical power analyses. Effects of aerobic exercise and fitness seem to mainly impact brain structures sensitive to neurodegeneration, which especially comprise frontal, temporal and parietal regions, such as the hippocampal/parahippocampal region, precuneus, anterior cingulate and prefrontal cortex, which are reported by several studies. General fitness measured via an objective fitness assessment and questionnaires seems to have a more global cerebral effect, probably due to its long-term application, whereas distinct intervention effects of durations between 3 and 6 months seem to concentrate on more local brain regions as the hippocampus, which can also be influenced by region of interest analyses. There is still a lack of evidence on other or combined types of intervention modalities, such as resistance, coordinative as well as multicomponent exercise during cognitive decline, and complex interventions as dancing. Future research should examine their beneficial effect on brain integrity, since several non-MRI studies already point to their advantageous impact. As a further future prospect, combination and application of newly developed imaging methods such as metabolic im...

The ventral striatum seems to play an important role during working memory (WM) tasks when irrelevant information needs to be filtered out. However, the concrete neural mechanisms underlying this process are still unknown. In this study, we investigated these mechanisms in detail. Eighteen healthy human participants were presented with multiple items consisting of faces or buildings. They either had to maintain two or four items from one category (low- and high-memory-load condition), or two from one category and suppress (filter out) two items from the other category (distraction condition). Striatal activity was increased in the distraction as compared with the high-load condition. Activity in category-specific regions in the inferior temporal cortex [fusiform face area (FFA) and parahippocampal place area (PPA)] was reduced when items from the other category needed to be selectively maintained. Furthermore, functional connectivity analysis showed significant reduction of striatal-PPA correlations during selective maintenance of faces. However, striatal-FFA connectivity was not reduced during maintenance of buildings vs. faces, possibly because face stimuli are more salient. Taken together, our results suggest that the ventral striatum supports selective WM maintenance by reduced gating of task-irrelevant activity via attenuating functional connectivity without increasing task-relevant activity correspondingly.

Background Physical activity has shown a positive impact on aging and neurodegeneration and represents a possible treatment option in cognitive decline. However, its underlying mechanisms and influences on brain pathology remain unclear. Dementia‐MOVE (Multi‐Objective Validation of Exercise) is a randomized‐controlled pilot trial, including 50 patients with amnestic cognitive impairment associated with Alzheimer's pathology, aiming to analyze the effect of physical activity and fitness on disease progression. Methods Dementia‐MOVE is divided into two arms, of either an intervention comprising physical activity, for at least twice a week, combined with a psychoeducational program, or a sole psychoeducational program. Physical activity intervention includes a supervised and unsupervised multimodal concept combining resistance, endurance, coordinative, and aerobic training. The primary outcome is the change of brain metabolism due to physical interventional treatment. Besides metabolic magnetic resonance imaging (MRI) including sodium and phosphorus imaging, resting state functional MRI, T1‐, T2‐weighted and fluid‐attenuated inversion recovery (FLAIR), as well as diffusion‐weighted imaging (DWI) of the brain and whole‐body fat MRI are performed before and after intervention, and will be compared in their sensitivity for the detection of intervention effects. We further assess cognitive performance, neuropsychiatric symptoms, quality of life, fitness, and sleep via questionnaires/interviews and/or fitness trackers, as well as microbiome, under the aspect of Alzheimer's pathology. Discussion The aim of Dementia‐MOVE is to investigate the effect of a multimodal exercise program on Alzheimer's pathology under different aspects of the disease. In this context, one of the main aims is the comparison of different MRI methods regarding their responsiveness for the detection of alterations induced by physical activity. As an underlying goal, new treatment and diagnostic options, as well as the exploration of fitness effects on brain structure and metabolism within a whole‐body perspective of Alzheimer's disease are envisaged.