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The purpose of this chapter is to provide a framework for approaching cognitive disorders based on anatomical localization and time course. In so doing we will review key clinical considerations in the diagnosis and management of conditions with acute/subacute onset versus those with insidious onset (Figure 20-1). In each case, it is important to know the cardinal features of the more common conditions as well as atypical features that should prompt consideration of alternative, less common conditions. For conditions with acute/subacute onset this involves understanding core aspects of delirium (exceedingly common) and features that might alternatively suggest conditions in the differential diagnosis of rapidly progressive dementia (RPD; relatively less common). For conditions with insidious onset, the chapter reviews a basic workup and considers a high-level distinction between two categories of presentations: nonprogressive disorders, and gradually progressive neurodegenerative (±vascular) diseases. Within the category of neurodegenerative disorders, we will explore the utility of a comprehensive diagnostic formulation encompassing syndrome, severity, and suspected underlying neuropathology. The chapter concludes by examining key elements of relatively more common conditions—late-onset, amnesic, and dysexecutive syndromes associated with underlying Alzheimer’s disease (AD) and Lewy body disease (LBD) neuropathology—and atypical features that might suggest relatively less common conditions such as non-amnesic presentations of AD and syndromes within the spectrum of frontotemporal lobar degeneration (FTLD) neuropathology.


Flowchart depicting major etiologic categories for cognitive disorders with acute/subacute onset or insidious onset. Specific conditions within these etiologic categories are reviewed in the text. Solid lines depict relatively more prevalent conditions, dashed lines less prevalent conditions. 1° tau, primary tauopathy; AD, Alzheimer’s disease; FUS, fused in sarcoma neuropathology; LBD, Lewy body disease; TDP-43, TDP-43 proteinopathy.


Cognitive disorders with acute and subacute manifestations evolving over hours, days, or weeks are frequently encountered in the inpatient setting due to their dramatic impact and requirement for urgent diagnosis and management. Distinguishing between delirium1 and RPD represents a key first step in determining the cause of cognitive dysfunction presenting acutely over days or weeks. The hallmarks of delirium include a primary disturbance in attention (including directing, focusing, sustaining, and shifting attention) representing a change from baseline and tending to fluctuate over the course of the day.1 Table 20-1 lists features used to distinguish delirium from RPD. Notably, delirium occurs most frequently from the indirect impact of underlying general medical conditions, medications, or drug intoxication or withdrawal on the brain as opposed to a primary neurological condition. It is critical to establish the presence of inattention via mental status examination and to assess for localizing signs via a targeted, efficient screening elemental neurological examination (see Chapter 5).

TABLE 20-1Features Distinguishing Delirium from Rapidly Progressive Dementia.

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