Brain Plasticity - Volume 4, issue 1

Authors: van Praag, Henriette

Article Type: Editorial

DOI: 10.3233/BPL-120418

Citation: Brain Plasticity, vol. 4, no. 1, pp. 1-2, 2018

Authors: Fernandez, A.M. | Santi, A. | Torres Aleman, I.

Article Type: Review Article

Abstract: The search for the cause of Alzheimer’s disease (AD), that affects millions of people worldwide, is currently one of the most important scientific endeavors from a clinical perspective. There are so many mechanisms proposed, and so disparate changes observed, that it is becoming a challenging task to provide a comprehensive view of possible pathogenic processes in AD. Tauopathy (intracellular neurofibrillary tangles) and amyloidosis (extracellular amyloid plaques) are the anatomical hallmarks of the disease, and the formation of these proteinaceous aggregates in specific brain areas is widely held as the ultimate pathogenic mechanism. However, the triggers of this dysproteostasis process remain …unknown. Further, neurofibrillary tangles and plaques may only constitute the last stages of a process of still uncertain origin. Thus, without an established knowledge of its etiology, and no cure in the horizon, prevention – or merely delaying its development, has become a last-resort goal in AD research. As with other success stories in preventive medicine, epidemiological studies have provided basic knowledge of risk factors in AD that may contribute to understand its etiology. Disregarding old age, gender, and ApoE4 genotype as non preventable risk factors, there are diverse life-style traits – many of them closely related to cardiovascular health, that have been associated to AD risk. Most prominent among them are diet, physical and mental activity, exposure to stress, and sleep/wake patterns. We argue that all these life-style factors engage insulinergic pathways that affect brain function, providing a potentially unifying thread for life-style and AD risk. Although further studies are needed to firmly establish a link between faulty insulinergic function and AD, we herein summarize the evidence that this link should be thoroughly considered. Show more

Keywords: Insulin peptides, life-style, risk of Alzheimer disease, diet, physical and mental activity, stress, sleep/wake cycle

DOI: 10.3233/BPL-180071

Citation: Brain Plasticity, vol. 4, no. 1, pp. 3-15, 2018

Authors: Vecchio, Laura M. | Meng, Ying | Xhima, Kristiana | Lipsman, Nir | Hamani, Clement | Aubert, Isabelle

Article Type: Review Article

Abstract: Physical activity plays an essential role in maintaining a healthy body, yet it also provides unique benefits for the vascular and cellular systems that sustain a healthy brain. While the benefit of exercise has been observed in humans of all ages, the availability of preclinical models has permitted systematic investigations into the mechanisms by which exercise supports and protects the brain. Over the past twenty-five years, rodent models have shown that increased physical activity elevates neurotrophic factors in the hippocampal and cortical areas, facilitating neurotransmission throughout the brain. Increased physical activity (such as by the voluntary use of a running …wheel or regular, timed sessions on a treadmill) also promotes proliferation, maturation and survival of cells in the dentate gyrus, contributing to the process of adult hippocampal neurogenesis. In this way, rodent studies have tremendous value as they demonstrate that an ‘active lifestyle’ has the capacity to ameliorate a number of age–related changes in the brain, including the decline in adult neurogenesis. Moreover, these studies have shown that greater physical activity may protect the brain health into advanced age through a number of complimentary mechanisms: in addition to upregulating factors in pro-survival neurotrophic pathways and enhancing synaptic plasticity, increased physical activity promotes brain health by supporting the cerebrovasculature, sustaining the integrity of the blood–brain barrier, increasing glymphatic clearance and proteolytic degradation of amyloid beta species, and regulating microglia activation. Collectively, preclinical studies demonstrate that exercise initiates diverse and powerful neuroprotective pathways that may converge to promote continued brain health into old age. This review will draw on both seminal and current literature that highlights mechanisms by which exercise supports the functioning of the brain, and aids in its protection. Show more

DOI: 10.3233/BPL-180069

Citation: Brain Plasticity, vol. 4, no. 1, pp. 17-52, 2018

Authors: Barha, Cindy K. | Liu-Ambrose, Teresa

Article Type: Review Article

Abstract: Engaging in targeted exercise interventions is a promising, non-pharmacological strategy to mitigate the deleterious effects of aging and disease on brain health. However, despite its therapeutic potential, a large amount of variation exists in exercise efficacy in older adults aged 55 and older. In this review, we present the argument that biological sex may be an important moderator of the relationship between physical activity and cognition. Sex differences exist in dementia as well as in several associated risk factors, including genetics, cardiovascular factors, inflammation, hormones and social and psychological factors. Different exercise interventions, such as aerobic training and resistance training, …influence cognition and brain health in older adults and these effects may be sex-dependent. The biological mechanisms underlying the beneficial effects of exercise on the brain may be different in males and females. Specifically, we examine sex differences in neuroplasticity, neurotrophic factors and physiological effects of exercise to highlight the possible mediators of sex differences in exercise efficacy on cognition. Future studies should address the potential sex difference in exercise efficacy if we are to develop effective, evidence-based exercise interventions to promote healthy brain aging for all individuals. Show more

Keywords: Exercise, sex differences, brain, cognition, aging, dementia, Alzheimer’s disease, neuroplasticity, neurotrophic factors, physical activity

DOI: 10.3233/BPL-180067

Citation: Brain Plasticity, vol. 4, no. 1, pp. 53-63, 2018

Authors: Barnes, Jill N. | Corkery, Adam T.

Article Type: Review Article

Abstract: The number of adults with Alzheimer’s disease (AD) or related dementia is expected to increase exponentially. Interventions aimed to reduce the risk and progression of AD and dementia are critical to the prevention and treatment of this devastating disease. Aging and cardiovascular disease risk factors are associated with reduced vascular function, which can have important clinical implications, including brain health. The age-associated increase in blood pressure and impairment in vascular function may be attenuated or even reversed through lifestyle behaviors. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on vascular health and cognition. Exercise …and cardiorespiratory fitness may be most important during midlife, as physical activity and cardiorespiratory fitness during the middle-aged years are associated with future cognitive function. The extent to which exercise, and more specifically aerobic exercise, influences the cerebral circulation is not well established. In this review, we present our working hypothesis showing how cerebrovascular function may be a mediating factor underlying the association between exercise and cognition, as well as discuss recent studies evaluating the effect of exercise interventions on the cerebral circulation. Show more

Keywords: Physical activity, cognition, blood pressure, blood flow, blood vessels

DOI: 10.3233/BPL-180075

Citation: Brain Plasticity, vol. 4, no. 1, pp. 65-79, 2018

Authors: Kelly, Áine M.

Article Type: Review Article

Abstract:  Alzheimer’s disease (AD), a progressive, neurodegenerative condition characterised by accumulation of toxic βeta-amyloid (Aβ) plaques, is one of the leading causes of dementia globally. The cognitive impairment that is a hallmark of AD may be caused by inflammation in the brain triggered and maintained by the presence of Aβ protein, ultimately leading to neuronal dysfunction and loss. Since there is a significant inflammatory component to AD, it is postulated that anti-inflammatory strategies may be of prophylactic or therapeutic benefit in AD. One such strategy is that of regular physical activity, which has been shown in epidemiological studies to be protective …against various forms of dementia including AD. Exercise induces an anti-inflammatory environment in peripheral organs and also increases expression of anti-inflammatory molecules within the brain. Here we review the evidence, mainly from animal models of AD, supporting the hypothesis that exercise can reduce or slow the cellular and cognitive impairments associated with AD by modulating neuroinflammation. Show more

Keywords: Exercise, microglia, astrocytes, neuroinflammation, Alzheimer’s disease

DOI: 10.3233/BPL-180074

Citation: Brain Plasticity, vol. 4, no. 1, pp. 81-94, 2018

Authors: Lin, Tzu-Wei | Tsai, Sheng-Feng | Kuo, Yu-Min

Article Type: Review Article

Abstract: Accumulating evidence indicates that exercise can improve learning and memory as well as attenuate neurodegeneration, including Alzheimer’s disease (AD). In addition to improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates systems like angiogenesis and glial activation that are known to support neuroplasticity. Moreover, exercise helps to maintain a cerebral microenvironment that facilitates synaptic plasticity by enhancing the clearance of Aβ , one of the main culprits of AD pathogenesis. The purpose of this review is to highlight the positive impacts of exercise on promoting neuroplasticity. Possible mechanisms involved in exercise-modulated neuroplasticity are …also discussed. Undoubtedly, more studies are needed to design an optimal personalized exercise protocol for enhancing brain function. Show more

Keywords: Exercise, neuroplasticity, dendrite, brain-derived neurotrophic factor, Alzheimer’s disease

DOI: 10.3233/BPL-180073

Citation: Brain Plasticity, vol. 4, no. 1, pp. 95-110, 2018

Authors: Llorens-Martín, María

Article Type: Review Article

Abstract: Alzheimer disease (AD) is the most common type of dementia in individuals over 65 years of age. The neuropathological hallmarks of the condition are Tau neurofibrillary tangles and Amyloid-β senile plaques. Moreover, certain susceptible regions of the brain experience a generalized lack of neural plasticity and marked synaptic alterations during the progression of this as yet incurable disease. One of these regions, the hippocampus, is characterized by the continuous addition of new neurons throughout life. This phenomenon, named adult hippocampal neurogenesis (AHN), provides a potentially endless source of new synaptic elements that increase the complexity and plasticity of the hippocampal …circuitry. Numerous lines of evidence show that physical activity and environmental enrichment (EE) are among the most potent positive regulators of AHN. Given that neural plasticity is markedly decreased in many neurodegenerative diseases, the therapeutic potential of making certain lifestyle changes, such as increasing physical activity, is being recognised in several non-pharmacologic strategies seeking to slow down or prevent the progression of these diseases. This review article summarizes current evidence supporting the putative therapeutic potential of EE and physical exercise to increase AHN and hippocampal plasticity both under physiological and pathological circumstances, with a special emphasis on neurodegenerative diseases and AD. Show more

Keywords: Adult hippocampal neurogenesis, neural plasticity, Alzheimer disease, neuroprotection, newborn granule neuron, memory

DOI: 10.3233/BPL-180065

Citation: Brain Plasticity, vol. 4, no. 1, pp. 111-126, 2018

Authors: Shepherd, Amy | Zhang, Tracy D. | Zeleznikow-Johnston, Ariel M. | Hannan, Anthony J. | Burrows, Emma L.

Article Type: Review Article

Abstract: Cognitive decline appears as a core feature of dementia, of which the most prevalent form, Alzheimer’s disease (AD) affects more than 45 million people worldwide. There is no cure, and therapeutic options remain limited. A number of modifiable lifestyle factors have been identified that contribute to cognitive decline in dementia. Sedentary lifestyle has emerged as a major modifier and accordingly, boosting mental and physical activity may represent a method to prevent decline in dementia. Beneficial effects of increased physical activity on cognition have been reported in healthy adults, showing potential to harness exercise and cognitive stimulation as a therapy in …dementia. ‘Brain training’ (cognitive stimulation) has also been investigated as an intervention protecting against cognitive decline with normal aging. Consequently, the utility of exercise regimes and/or cognitive stimulation to improve cognition in dementia in clinical populations has been a major area of study. However, these therapies are in their infancy and efficacy is unclear. Investigations utilising animal models, where dose and timing of treatment can be tightly controlled, have provided many mechanistic insights. Genetically engineered mouse models are powerful tools to investigate mechanisms underlying cognitive decline, and also how environmental manipulations can alter both cognitive outcomes and pathology. A myriad of effects following physical activity and housing in enriched environments have been reported in transgenic mice expressing Alzheimer’s disease-associated mutations. In this review, we comprehensively evaluate all studies applying environmental enrichment and/or increased physical exercise to transgenic mouse models of Alzheimer’s disease. It is unclear whether interventions must be applied before first onset of cognitive deficits to be effective. In order to determine the importance of timing of interventions, we specifically scrutinised studies exposing transgenic mice to exercise and environmental enrichment before and after first report of cognitive impairment. We discuss the strengths and weaknesses of these preclinical studies and suggest approaches for enhancing rigor and using mechanistic insights to inform future therapeutic interventions. Show more

Keywords: Dementia, exercise, physical activity, environmental enrichment, ‘brain training’, cognitive stimulation, lifestyle factors, experience-dependent plasticity, enviromimetics

DOI: 10.3233/BPL-180076

Citation: Brain Plasticity, vol. 4, no. 1, pp. 127-150, 2018