Swallowing is a coordinated activity that allows the uninterrupted passage of oral contents (food, saliva, or secretions) into the stomach. Any disorder in the swallowing process that presents a risk of penetration/aspiration is called dysphagia. The term oropharyngeal dysphagia is used when alterations are characterized by impairment in the oral and pharyngeal phases of swallowing. Oropharyngeal dysphagia is a symptom with high prevalence and severity in patients with Parkinson's disease (PD) and impairs the safe swallowing of food or saliva, leading to risks such as dehydration, malnutrition, and aspiration pneumonia, and even mortality.

Diffusion-weighted imaging of the brain allows the direct detection of water diffusion in the brain and, therefore, the imaging of white matter fibers. Thus, this imaging has become the preferential tool to investigate brain connectivity. In particular, thanks to the spread of accurate algorithms for fiber reconstruction, recent tractography studies outlined how neurodegenerative diseases such as Alzheimer's disease (AD) would affect the brain. Tractography studies use the graph theory mathematical framework to characterize how different anatomical regions are connected within the brain. In addition, it is possible to investigate the number of connections and their intensity, the brain organization, and the information flow. Results demonstrate that AD is a disruption disease, in that it impairs the brain connectivity and its organization. Future research goals are to summarize this information and eventually combine it with other imaging sources into a robust framework for early diagnosis of AD.

Vascular dementia is claimed to be the second most common cause of dementia, accounting for ∼15%–20% of cases. Clinical diagnosis is challenging because with the term “vascular dementia” we consider different vascular pathologies, such as multiinfarct dementia, small vessel disease, strategic infarct dementia, hypoperfusion dementia, hemorrhagic dementia, hereditary vascular dementia, and Alzheimer's disease with cardiovascular disease. Nowadays there is still a lack of consensus regarding disease classification and diagnostic criteria. Although there has been much progress in defining and understanding the relation between cerebrovascular disease and dementia, some uncertainties remain. There is a lot of evidence supporting an interaction between Alzheimer's and vascular pathology, but the relation between the two pathologies has not yet been completely understood. For the correct management of vascular dementia, primary and secondary prevention measures for the causative cerebrovascular disease, such as vascular risk factors intervention and antiplatelet and anticoagulation therapies, are important. However, unlike Alzheimer's disease, there are no established symptomatic treatments for cognitive impairment.

Epidemiological evidence suggests a high level of cognitive engagement, particularly in early life, is associated with a reduced risk of developing dementia in later life, including that caused by Alzheimer's disease. Limitations inherent in epidemiological investigations means that the mechanisms underlying this putative relationship are not well understood, and the array of extraneous factors encountered over a person's life span cannot be controlled for. In this regard, environmental enrichment is used as an experimental paradigm to model the effect of stimulation from the environment on animal models. Given that compelling evidence suggests that the adult brain has the capacity to undergo environment-induced plasticity, stimulation from the environment is suggested to act preventatively toward Alzheimer's disease. The focus of this review is on the pathological and functional outcomes of both preventative and therapeutic environmental enrichment on commonly used mouse models of amyloid pathology.

Alzheimer's disease assessment can reveal multiple pathophysiological lesions and changes concerning age, comorbidities, and dysregulation in nutritional intake as well as behavioral and cognitive abnormalities including dementia and mild cognitive impairment. Up to now, many potential biomarkers and risk factors have been presented as independent diagnostic guidelines, but none have yet suggested a standardized method with 100% prediction accuracy. Unfolded proteins, the overexpression of amyloid beta causing neuronal apoptosis and alteration in mitochondrial dynamics, the interaction of amyloid beta and tau proteins, and the neurofibrillary tangles strongly related to cognitive decline are commonly under investigation using cerebrospinal fluid analysis, structural and functional neuroimaging, and other electrophysiological tests related to Alzheimer's disease. All these tests have supported the implementation of several tools for the early diagnosis or prediction of Alzheimer's disease based mainly on computational tools like virtual physiological human models, expert decision support systems like geriatric assessment programs, statistical methods like Bayesian networks, or artificial intelligence algorithms. While there is no holistic treatment for Alzheimer's disease or a single fingerprint test, early diagnosis and prediction of the disease is an efficient solution. This chapter focuses on the latest advances as well as various applications/tools for Alzheimer's disease prediction.

Overall, acute hospital service activity currently attributable to caring for people with dementia is already considerable, and this is likely to increase significantly in coming decades.

Amyloid positron emission tomography (PET) imaging with [11C]-PIB, which has high affinity for fibrillar Aβ, detects Aβ deposition in the brain and is a distinctive and reliable biomarker of Alzheimer's disease (AD) [18F]-labeled amyloid PET imaging, including [18F]-florbetapir, [18F]-flutemetamol, and [18F]-florbetaben, has recently been approved and replaces [11C]-PIB PET imaging in clinical practice. The procedures of amyloid PET imaging are performed according to protocol. In postmortem histopathology, these amyloid tracers have been shown to bind to Aβ plaques. Amyloid PET imaging can distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. The diagnostic accuracy has been evaluated with visual and quantitative analysis. Amyloid PET imaging differentiated AD patients from healthy control subjects with a high degree of sensitivity and specificity. In addition, subjects with cognitively normal or mild cognitive impairment (MCI) progressed to MCI or AD dementia, respectively, when Aβ deposition was identified by amyloid PET imaging. Amyloid PET imaging can identify the status of the Aβ deposition of the underlying AD pathophysiology, increase diagnostic certainty, and alter management. In the predementia phase of AD, amyloid PET imaging can predict progression to AD dementia.

Since 2000, a plethora of transgenic mouse models have been developed to reproduce the main features of Alzheimer's disease (AD). Due to the complexity of the disease, no ideal animal model exists to date. The 5×FAD mouse line recapitulates numerous neuropathological insults and cognitive alterations found in human AD patients: from amyloid deposits to intense gliosis and neuroinflammation, including neurotransmission alteration, synaptic loss, neurodegeneration, and behavioral and memory deficits. The extremely aggressive amyloid pathology of these mice makes them a suitable model for early-onset AD. This chapter describes and illustrates the main characteristics of the 5×FAD mouse model and discusses its usefulness in the context of preclinical evaluation of drug candidates or promising therapeutic targets against AD.

The term “frontotemporal dementia” (FTD) defines a group of related diseases resulting from progressive degeneration of the temporal and frontal lobes. These areas play a significant role in decision-making, behavioral control, emotion, language, and motor functions. FTD has a strong genetic component, with approximately 10% of cases showing an autosomal dominant transmission of the phenotype (aFTD). Genetic variants in the MAPT, GRN, and C9orf72 genes are the most frequent causes of aFTD. Mutations in a number of other rare genes have been also described. Studies investigating the genotype–phenotype correlations suggest that gene defects may present clinical phenotypes that are partially distinct. MAPT gene mutations generally present an FTD behavioral phenotype, frequently associated with extrapyramidal symptoms. GRN mutations are frequently characterized by psychiatric symptoms, like hallucinations and delusions, associated with language dysfunction and parkinsonism. Finally, patients carrying C9orf72 repeat expansions present with behavioral disturbances, psychotic symptoms, and motor neuron disease. In this chapter, available data regarding the effects of genetic variants on the clinical and pathological characteristics of aFTD will be discussed.

Alzheimer's disease is a complicated neurodegenerative disorder. It is characterized by the pathological accumulation of amyloid-β peptides and neurofibrillary tangles within the brain, which leads to severe cognitive damage. Studies indicate that retinoid signaling in the brain might have crucial impacts on the pathogenesis of Alzheimer's disease. All-trans retinoic acid is an active metabolite of vitamin A in the brain and has been argued to have beneficial effects in Alzheimer's disease. In this chapter, the latest findings on the potential prophylactic and therapeutic effects of retinoid signaling on Alzheimer's disease will be described. Meanwhile, developing insights into possible mechanisms by which retinoic signaling in the brain modulate aspects of Alzheimer's disease will be discussed.