What Is the Clinical Course of Advanced Dementia?

Introduction and Scope of the Problem

Dementia is a clinical syndrome associated with significant changes in cognition, behavior, and functional status. It is characterized by the development of multiple cognitive and behavioral impairments involving at least two of the following domains: (1) memory, (2) executive function (reasoning, planning, judgment), (3) visuospatial ability, (4) language, (5) and personality or behavior. Importantly, the decline in cognitive abilities must be severe enough to interfere with social or occupational functioning and cannot be accounted for by other psychiatric conditions such as depression.

It is currently estimated that 24 million people worldwide have dementia. The incidence increases with age, rising from 5% in those aged 71 to 79 years to more than 30% in those aged 90 and older. Alzheimer’s disease represents the majority of these cases, accounting for over 50%. Others include vascular dementia, Lewy body dementia, dementia related to Parkinson’s disease, and frontotemporal dementia. These different types of dementia are associated with distinct symptom patterns, but overlap often exists ( Table 41.1 ).

For the vast majority of dementias, the clinical course is relentlessly progressive, irreversible, and ultimately fatal. Initially, the decline in cognition may manifest itself as behavioral and mood changes, as well as the inability to perform instrumental activities of daily living, such as managing medications, using the telephone, shopping, and handling finances. In the end stage of the disease, the different dementia syndromes can appear very similar, with individuals losing the ability to communicate, recognize loved ones, and ambulate. These individuals have a very poor prognosis and are likely to experience a high burden of illness such as dysphagia, aspiration pneumonia, and weight loss, as well as having increased risk for multiple burdensome interventions.

Relevant Pathophysiology

The accumulation of extracellular amyloid plaques, formation of intracellular neurofibrillary tangles, and loss of neurons are characteristic findings seen at autopsy in individuals with advanced Alzheimer’s disease. Amyloid plaques are likely the result of abnormal metabolism of amyloid-β 40 and 42 (referring to the amyloid peptide length), leading to plaque accumulation. These plaques accumulate in areas of the brain responsible for learning and memory, most notably the hippocampus and entorhinal cortex. Neurofibrillary tangles consist mainly of hyperphosphorylated tau protein, a microtubule assembly protein. The mechanism for neuronal death and its relationship to neuritic plaques and neurofibrillary tangles continues to be an area of great controversy, because these pathological findings can be observed at autopsy in older adults who had no clinical evidence of dementia during their lifetime. More research is needed to distinguish whether plaques and tangles are the mediators or the by-products of the pathogenesis of Alzheimer’s disease.