Biomarkers are objectively measured characteristics of a biologic or pathogenic process, which can have a variety of applications, including diagnosing disease and measuring response to therapeutic interventions. Historically, the diagnosis of dementing neurodegenerative diseases has relied on clinical characterization of patients during life, using established clinical diagnostic criteria to assign the diagnosis that best matches the patient’s phenotype, and later performing postmortem brain autopsy to make a definitive diagnosis. Biomarkers have been developed to measure pathophysiological changes that are hallmarks of different neurodegenerative diseases. For example, in Alzheimer’s disease (AD), biomarkers can detect and measure the two pathological hallmarks, amyloid plaques and tau tangles, in living people, using PET, CSF, or plasma testing. Biomarkers have the potential to redefine the diagnosis of AD and neurodegenerative diseases as biological processes rather than as clinical entities. Biomarkers will transform our ability to evaluate and treat neurodegenerative diseases by improving diagnostic accuracy.

Cognitive assessment is used to detect, characterize, and monitor the degree of cognitive impairment in dementia and its earlier stages. Brief cognitive assessments are frequently used across diverse clinical settings and offer scalability as a frontline marker aimed at enhancing the clinical efficiency of diagnostic work-up. These tools have a potential to facilitate early detection and diagnosis of symptomatic cognitive impairment, which is a crucial first step to providing medical and supportive care that benefits people with cognitive impairment and their care partners and for identifying pre-surgical or hospitalized patients who may benefit from delirium prevention interventions. This chapter provides an overview of the most commonly used brief cognitive measures in clinical practice, recent developments and novel measures, and future directions for use of brief cognitive tools across clinical settings including primary, dementia specialist, preoperative, and inpatient care. Recommendations for cultural considerations and optimal implementation paradigms are also discussed.

Alzheimer’s disease typically manifests age 65 or older with a predominant memory dysfunction followed by a progressive impairment of other cognitive domains. Aging is the main risk factor for AD development. However, up to 10% of patients present an early onset (under 65), manifesting more frequently with atypical phenotypes. Amyloid plaques and neurofibrillary tangles due to tau deposition are the main hallmarks of the disease. Despite sharing the same neuropathological features, AD phenotypes present differential tau distribution patterns in cortical areas, being tau-pathology topographically related to the clinical syndrome. In addition to aging, several other factors may contribute to AD pathology and its clinical expression. AD is currently understood as a disease continuum starting with a preclinical phase, progressively leading to mild cognitive impairment and dementia. The development of biological and neuroimaging biomarkers detecting in vivo the defining features of AD has remarkably improved the accuracy and early diagnosis of AD in the last decades.

This chapter focuses on the challenges and experiences of caregiving in dementia, emphasizing the importance of protecting caregiver health and well-being. It discusses effective communication strategies, provides a list of useful web-based educational resources for caregivers, and explores direct and indirect caregiver support interventions. The chapter highlights the need for better support and resources for caregivers, including access to respite care and palliative care services. It also provides strategies for healthcare providers to better engage and support caregivers. Overall, the chapter emphasizes the need to prioritize caregiver health and well-being in dementia care to improve outcomes for both caregivers and individuals with dementia.

Alzheimer’s disease (AD) is the most common type of dementia, accounting for approximately 60% of dementia cases (either alone or in combination); vascular dementia (VaD) accounts for another 10–20%. Most epidemiologic research on dementia has examined prevalence, incidence, and risk factors for either all-cause dementia or AD. This chapter discusses the epidemiology of all-cause dementia and AD, as well as advancement in VaD-related risk factors. Numerous prospective, observational studies have identified a variety of factors that may prevent or delay dementia onset. To better understand the epidemiology of dementia and the potential benefits of implementing interventions, future studies need to address the life course and long preclinical aspects of this disorder. More work is needed to understand the epidemiology and risk factors for non-AD or VaD dementias.

This chapter discusses the neuropathology of dementia, focusing on the degenerative dementia syndromes commonly encountered by dementia specialists. It highlights the concept of selective vulnerability, where specific neuron types in specific brain regions decline and die, leading to progressive dysfunction. Alzheimer’s disease (AD) is the most prevalent cause of dementia, characterized by neurofibrillary pathology and the presence of neuritic plaques and neurofibrillary tangles. Dementia with Lewy Bodies (DLB), multiple system atrophy (MSA), and frontotemporal dementia (FTD) are also discussed, along with their respective clinical features and underlying pathology. The chapter emphasizes the complexity of neurodegenerative diseases and the need for more integrative models to understand their pathogenesis and develop effective therapies.

The population of people over the age of 80 is increasing in nearly all regions of the world. Age is tightly linked to the prevalence of dementia and is also linked to the frequency of protein deposition that does not meet neuropathological criteria for dementias, sometimes of unclear recognized importance. Among those over the age of 80, Alzhiemer’s disease remains the most common neuropathology with or without cerebrovascular disease or other co-pathology. Comorbid pathology is increasingly common in older age. The frequency of pure vascular dementia diminishes with age. The tight neuropathological to clinical correlates of dementia seen in younger populations are not as strong in the oldest-old where individuals without dementia oftern demonstrate substantial disease-specific neuropathology and those with dementia sometimes don’t evidence expected neuropathology. In addition to covering these concepts, new entities including Aging-related Tau Astrogliopathy (ARTAG), Limbic Predominant Age-related TDP-43 Proteinopathy (LATE) and Primary Age-related Tauopathy (PART) are briefly discussed.

This chapter discusses the diagnostic evaluation, physical examination, initial diagnostic formulation, investigations, and management of individuals with cognitive and/or behavioral changes. It emphasizes the importance of obtaining a comprehensive history from the patient and an informant, as well as conducting a thorough physical examination. The chapter also provides sample questions for assessing different cognitive domains and lists clues that suggest a non-Alzheimer’s disease etiology of cognitive/behavioral changes. It suggests various diagnostic studies and consultations that may be necessary for each patient. The document highlights the principles of management, including treating reversible causes, minimizing psychoactive medications, promoting regular sleep and exercise, and providing caregiver support. It also discusses the availability of pharmacologic therapies and the importance of providing information and support to families facing dementia-related issues.