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Depression is the most highly prevalent neuropsychiatric syndrome across all neurologic illnesses (Fig. 5-1). The relationship between depression and neurologic illness is complex in several aspects, including pathophysiology, clinical presentation, and response to treatment. Depression may sometimes be the direct result of brain pathology, very much like other neurological manifestations, such as cognitive or motor disturbances. In other cases, a more complex interplay of neurobiological, environmental, and coping mechanisms appears responsible for the development of depressive symptoms (Box 5-1). Neurologic illness may produce signs and symptoms that mimic depression, such as psychomotor retardation, apathy, concentration deficits, and sleep disorders, making the diagnosis of depression in the context of neurologic illness challenging. However, the identification and treatment of depression in these individuals is of fundamental importance, as this tends to improve the prognosis of the neurological disease.

Figure 5-1

Mean risk of depression for selected illnesses (% prevalence for particular disease.)



Living alone

Social stress


Personal or family history of depression

Physical impairment

Cognitive impairment

Alcohol and substance use disorders



Cerebrovascular disease

Cortical and subcortical atrophy

Lesions of left frontal lobe, basal ganglia

Frontal and temporal lesions; atrophy and hypointense lesion burden (MS)

Other specific lesions (see Fig. 5-2)

Figure 5-2

Localization-based clinical phenomena underlying brain-behavior relationships in traumatic brain injury.

This chapter covers depression in the context of specific neurological disorders, such as dementia, cerebrovascular disease, Parkinson disease (PD) and other movement disorders, multiple sclerosis, traumatic brain illness, and epilepsy. Depression in the context of pain is covered in Chapter 21 and depression in the context of a sleep disorder is covered in chapter 22.

See Figure 5-1 and Box 5-1 for prevalence and risk factors of depression in different neurological illnesses.


“Dementia” refers to a syndrome characterized by cognitive deterioration, behavioral abnormalities, and possible personality changes that significantly affect daily functioning. A dementia syndrome can be caused by myriad etiologies, including neurodegenerative processes, such as Alzheimer disease (AD), dementia with Lewy bodies, and frontotemporal dementia, cerebrovascular disease, traumatic brain injury (TBI), infectious illnesses such as HIV, and other neurologic disturbances. This section covers depression in dementia secondary to a neurodegenerative process, with emphasis on depression in AD. Depression refers to clinically significant depressive symptoms, rather than particular subtypes as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) unless otherwise noted. Cerebrovascular depression and depression associated with PD are addressed later in this chapter.


Neuropsychiatric symptoms are common in dementia, and depression is one of the most frequent manifestations.1,2 Much of the research ...

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