Humans ; AIDS Dementia Complex/pathology* ; HIV Infections

Dementia ; pathology ; Hallucinations ; pathology ; Humans ; Lewy Body Disease ; pathology ; Nerve Net ; pathology

Alzheimer's disease (AD) is characterized by decreased neuronal activity and atrophy, while hyperactivity of neurons seems to make them resistant to aging and neurodegeneration, a phenomenon which we have paraphrased as 'use it or lose it'. Our hypothesis proposes that (1) during their functioning, neurons are damaged; (2) accumulation of damage that is not repaired is the basis of aging; (3) the vulnerability to AD is determined by the genetic background and the balance between the amount of damage and the efficiency of repair, and (4) by stimulating the brain, repair mechanisms are stimulated and cognitive reserve is increased, resulting in a decreased rate of aging and risk for AD. Environmental stimulating factors such as bilingualism/multilingualism, education, occupation, musical experience, physical exercise, and leisure activities have been reported to reduce the risk of dementia and decrease the rate of cognitive decline, although methodological problems are present.
Animals ; Brain ; pathology ; physiopathology ; Dementia ; genetics ; pathology ; physiopathology ; prevention & control ; Humans ; Models, Neurological

Brain ; pathology ; Dementia ; pathology ; Gene Expression ; physiology ; Genome-Wide Association Study ; Humans

PURPOSE: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. METHODS: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 µg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. RESULTS: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. CONCLUSION: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.
Animals ; Atrophy ; Carotid Artery, Common ; Corpus Callosum ; Dementia ; Dementia, Vascular ; Demyelinating Diseases ; Ghrelin ; Hippocampus ; Humans ; Learning ; Memory Disorders ; Memory ; Microvessels ; Models, Animal ; Molecular Biology ; Myelin Sheath ; Neuroprotection ; Pathology ; Rats ; Spatial Memory ; Vascular Endothelial Growth Factor A ; Water ; White Matter

BACKGROUND AND PURPOSE: Semantic memory remains more stable than episodic memory across the lifespan, which makes it potentially useful as a marker for distinguishing pathological aging from normal senescence. To obtain a better understanding of the transitional stage evolving into Alzheimer's dementia (AD), we focused on the amnestic mild cognitive impairment (aMCI) stage stratified based on β-amyloid (Aβ) pathology. METHODS: We analyzed the raw data from Korean version of the Boston Naming Test (K-BNT) and the Controlled Oral Word Association Test (COWAT). For K-BNT, the frequencies of six error types and accuracy rates were evaluated. For a qualitative assessment of the COWAT, we computed the number of switching, number of clusters, and mean cluster size. RESULTS: The data from 217 participants were analyzed (53 normal controls, 66 with Aβ− aMCI, 56 with Aβ+ aMCI, and 42 disease controls). There were fewer semantically related errors and more semantically unrelated errors on the K-BNT in Aβ+ aMCI than in Aβ− aMCI, without a gross difference in the z score. We also found that Aβ+ aMCI showed a more prominent deficit in the number of clusters in the semantic fluency task [especially for animal names (living items)] than Aβ− aMCI. CONCLUSIONS: In spite of similar clinical manifestations, Aβ+ aMCI was more similar to AD than Aβ− aMCI in terms of semantic memory disruption. Semantic memory may serve as an early indicator of brain Aβ pathology. Therefore, semantic memory dysfunction deserves more consideration in clinical practice. Longitudinal research with the follow-up data is needed.
Aging ; Alzheimer Disease ; Animals ; Brain ; Dementia ; Follow-Up Studies ; Humans ; Memory* ; Memory, Episodic ; Mild Cognitive Impairment* ; Pathology ; Semantics* ; Word Association Tests

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.
alpha-Synuclein ; Animals ; Brain ; Central Nervous System ; Dementia ; Lewy Bodies ; Models, Animal ; Multiple System Atrophy ; Neurodegenerative Diseases ; Parkinson Disease ; Pathology

Due to the progressive aging of Korean society and the introduction of brain banks to the Korean medical system, the possibility that pathologists will have access to healthy elderly brains has increased. The histopathological analysis of an elderly brain from a subject with relatively well-preserved cognition is quite different from that of a brain from a demented subject. Additionally, the histology of elderly brains differs from that of young brains. This brief review discusses primary age-related tauopathy; this term was coined to describe elderly brains with Alzheimer’s diseasetype neurofibrillary tangles mainly confined to medial temporal structures, and no β-amyloid pathology.
Aged ; Aging ; Amyloid beta-Peptides ; Autopsy ; Brain ; Cognition ; Dementia ; Humans ; Neurofibrillary Tangles ; Numismatics ; Pathology ; Tauopathies

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.
Brain ; Cognition ; Dementia, Vascular ; Energy Metabolism ; Fasting ; Glucose ; Insulin Resistance ; Life Style ; Metabolism ; Methods ; Pathology ; Risk Factors

Type 2 diabetes (T2D) increases the risk for cerebrovascular disease (CVD) and dementia. The underlying molecular mechanisms remain elusive, which hampers the development of treatment or/and effective prevention strategies. Recent studies suggest that dyshomeostasis of amylin, a satiety hormone that forms pancreatic amyloid in patients with T2D, promotes accumulation of amylin in cerebral small blood vessels and interaction with Alzheimer's disease (AD) pathology. Overexpression of human amylin in rodents (rodent amylin does not form amyloid) leads to late-life onset T2D and neurologic deficits. In this Review, we discuss clinical evidence of amylin pathology in CVD and AD and identify critical characteristics of animal models that could help to better understand molecular mechanisms underlying the increased risk of CVD and AD in patients with prediabetes or T2D.
Alzheimer Disease ; Amyloid ; Blood Vessels ; Cerebrovascular Disorders ; Dementia ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Humans ; Islet Amyloid Polypeptide ; Models, Animal ; Neurologic Manifestations ; Pathology ; Prediabetic State ; Rodentia