Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome primarily affecting the parietal and occipital lobes. It is characterized by early deficits in visuospatial processing, numeracy, and literacy. The most common underlying pathology is Alzheimer’s disease (AD). PCA typically presents as a young onset form of dementia, with the majority of patients aged 50–65 years. The clinical presentation of PCA includes difficulties with visually and spatially complex tasks. Neuropsychological features include impairments in visuospatial and visuoperceptual processing. Neuroimaging studies show occipito-parietal atrophy and hypometabolism . There is limited evidence of a genetic component in PCAs. Pathologically, PCA is most commonly associated with AD. The consensus classification of PCA provides a framework for improved diagnosis and research. PCA shows overlap with other atypical AD presentations, and there is heterogeneity within the syndrome. The impact of PCA on everyday abilities and the subjective experience of individuals with PCA is not well understood. Management and support for PCA include pharmacological and nonpharmacological approaches .

Lewy body disease (LBD) can present as a dementia-predominant syndrome with parkinsonism (dementia with Lewy bodies or DLB), a motor-predominant syndrome with subsequent dementia ( Parkinson’s disease with dementia or PDD), or an autonomic-predominant syndrome (multiple system atrophy or MSA); this chapter focuses on treatment/management of the many complex manifestations of DLB. Education and support are important in managing DLB. Currently, there is no therapy that significantly alters the underlying pathophysiology of DLB. This chapter covers the management of cognitive impairment, neuropsychiatric features, motor dysfunction, sleep disorders, and autonomic dysfunction. Acetylcholinesterase inhibitors (AChEI) can improve cognition. Memantine may provide modest benefit. Medications such as clozapine or quetiapine can help manage visual hallucinations and delusions. Carbidopa/levodopa and dopamine agonists can improve motor symptoms, but caution is needed. Clonazepam, melatonin, and psychostimulants can address sleep issues. Orthostatic hypotension can be managed with lifestyle changes and medications.

The brain neuromodulatory systems consist of small regions in the brainstem, pontine nucleus, and basal forebrain that regulate cognitive behavior by releasing neurotransmitters. Ascending projections from the brainstem and basal forebrain regions spread these neurotransmitters to broad areas of the central nervous system within the frontal cortex, anterior cingulate, or hippocampus, signaling a range of neural pathways. The modulator effect executed in these brain areas, together with the interplay between the systems, is crucial for regulating and adjusting many cognitive and behavioral functions. Neurodegenerative disease processes frequently affect the normal functioning of these modulator circuitries, directly leading to or contributing to the appearance of cognitive and neuropsychiatric symptoms. Even though these neuromodulatory systems’ impairment and imbalance happen early, further efforts to understand better their neurobiological basis are warranted . Hence, this chapter aims to review the role of the neuromodulatory systems in behavior and cognition and how their dysfunction shapes the neurodegenerative dementia phenotype.

Neuropsychiatric symptoms (NPS) are prevalent in dementia and can include depression, anxiety, agitation, aggression, disinhibition, apathy, psychosis, compulsions, eating disorders, and sleep disturbances. These symptoms can occur at different stages of the disease and vary in frequency and severity between different types of dementia. The underlying pathology of each disease can affect different brain structures, leading to overlapping symptoms and syndromes. Treatment options for NPS are limited and often based on trial and error. Nonpharmacological interventions, such as cognitive behavioral therapy and lifestyle modifications, can be effective in some cases. Pharmacological interventions, including antidepressants, antipsychotics, and stimulants, may also be used, but their efficacy is variable, and they can have side effects. Further research is needed to better understand the underlying mechanisms of NPS in dementia and to develop more effective treatment strategies.

Treatment of Alzheimer’s disease (AD) requires a complex interaction among the patient and care partner, clinician, and health care system. Pharmacotherapy for AD includes aducanumab for patients with mild cognitive impairment mild AD dementia due to AD. Cholinesterase inhibitors are available for mild, moderate, and severe AD dementia and memantine is indicated for patients with moderate and severe AD dementia. Neuropsychiatric symptoms – agitation, psychosis, depression, apathy, insomnia – are common in AD and can be managed with psychotropic agents. Most use of psychotropics is off label and based on the phenotypic similarity between the symptoms occurring in AD and those occurring in disorders with approved indications. The first disease modifying agents for AD are moving toward clinical use in prodromal AD/mild AD dementia. These agents will make new demands on clinicians, health care systems, and patients and their care partners. Pharmacotherapy of AD is combined with recommendations for a brain-healthy lifestyle and care of the care partner.

This chapter provides an overview of chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head trauma. It discusses the historical background of CTE, its neuropathology, clinical features, and epidemiology. The chapter also explores the current understanding of CTE staging and common co-pathologies. It highlights the challenges in diagnosing and monitoring CTE in living patients and the ongoing research efforts to develop biomarkers for early detection. The chapter concludes by discussing the prevention, treatment, and future directions in CTE research. It is important to recognize the risks of head trauma and implement measures to reduce the incidence of CTE and other neurodegenerative diseases associated with head trauma.

Delirium is an acute disturbance in mental status characterized by fluctuations in cognition and attention that affects more than 2.6 million hospitalized older adults in the United States annually, a rate that is expected to increase with the aging population. Delirium is associated with a myriad of poor outcomes, including prolonged hospital stay and readmission, loss of independence, new or accelerated cognitive impairment, and death. The relationship between delirium and dementia is complex, as dementia is one of the most significant risk factors for delirium, and delirium is independently associated with an increased risk of subsequent cognitive decline. Here, we provide a current review on the epidemiology, evaluation and management of older adults with delirium, focusing on those instances where it can be mistaken for a dementing illness.

Mild cognitive impairment (MCI) is a clinical syndrome characterized by cognitive changes from previous levels of performance, often seen as a transitional state between normal aging and dementia. It can be caused by various factors such as Alzheimer’s disease, Lewy body disorders, vascular disease, and other neurodegenerative conditions. The prevalence of MCI increases with age, and the progression rate to dementia is approximately 15-20% per year. Pharmacologic treatments for MCI, particularly those targeting Alzheimer’s disease, have limited efficacy. Non-pharmacologic interventions like aerobic exercise and cognitive stimulation may have some benefits. Biomarkers, particularly plasma markers, are being used to diagnose and predict the progression of MCI to dementia. A combination of biomarkers like P-tau 181 and NfL has shown promise in predicting progression. MCI remains a useful construct in clinical practice and research for identifying individuals at risk of cognitive decline and dementia.

The behavioral variant of frontotemporal dementia (bvFTD) is a clinical syndrome characterized by progressive deterioration of social behavior and cognitive functions. It is one of the most common causes of early-onset dementia and is associated with frontotemporal lobar degeneration (FTLD). The diagnosis of bvFTD can be challenging due to its overlap with other psychiatric disorders, but obtaining a detailed clinical history from a reliable informant is essential. Diagnostic criteria for bvFTD include behavioral and cognitive features such as loss of motivation, social disinhibition, lack of empathy, repetitive behaviors, changes in eating habits, and executive dysfunction. Biomarkers such as brain imaging and genetic testing can help increase diagnostic certainty. Disease progression in bvFTD leads to disability and functional deterioration. Future research aims to improve early recognition, diagnostic accuracy, and the development of disease-modifying treatments.