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 ).

Table 41.1
Dementia Syndromes and Key Features
Type of Dementia Characteristics
Alzheimer’s disease
  • Most common type of dementia

  • Memory impairment, with difficulty remembering names and recent events often seen early in the disease

  • Impaired behavior changes and difficulty speaking, swallowing, and walking seen later in the disease

  • Deposition of beta-amyloid (plaques) and tau (tangles) in brain

Vascular dementia
  • Second most common type of dementia

  • Criteria for dementia occurring in the setting of historical, physical, or neuroimaging evidence of cerebrovascular disease

  • May present as an abrupt deterioration in cognitive function or in a fluctuating, stepwise manner

Mixed dementia
  • Disease progression and pattern similar to that of Alzheimer’s disease and vascular dementia

Lewy body dementia
  • Progressive cognitive decline accompanied by well-formed visual hallucinations, parkinsonism, and fluctuating levels of alertness

  • Notable sensitivity to neuroleptic medications

  • Insoluble α-synuclein aggregations in brain are a key pathological feature

Parkinson’s disease
  • Distinguished by dementia occurring in the setting of well-established Parkinson’s disease rather than before or soon after parkinsonian symptoms developed

Frontotemporal dementia
  • A heterogeneous disorder characterized by focal atrophy of the frontal and temporal lobes

  • Prominent features include personality and behavior change, with inappropriate social conduct, early loss of insight, and blunted emotional responses

  • Often seen in individuals younger than those with Alzheimer’s disease

Normal pressure hydrocephalus
  • Pathologically enlarged ventricular size with normal opening pressures on lumbar puncture

  • Associated with a classic triad of dementia, gait disturbance, and urinary incontinence

  • Potentially reversible by the placement of a ventriculoperitoneal shunt

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.

Classifying the Severity of Dementia

Decline in cognitive and functional ability in Alzheimer’s dementia can be viewed as passing through stages, although significant variation occurs among individuals and types of dementia. In mild dementia, individuals often have impairments with recent memories and difficulties with complex tasks, such as managing financial affairs. As the disease progresses, individuals lose cognitive and physical function. They begin to have problems with disorientation, often getting lost in familiar places, and have increasing difficulty recognizing family and friends. Moderate dementia is commonly associated with significant deficits with complex tasks and an increased need for assistance with basic activities of daily living. In the most advanced stages, individuals with dementia become completely dependent on others, often requiring around-the-clock care. Loss of the ability to ambulate independently, to communicate with others, and to eat without assistance is characteristic of the end stage of the disease. The predominant functional trajectory for these individuals is a persistently severe disability, in which they are completely dependent in basic activities of daily living throughout the last year of life.

Staging the severity of dementia may be aided by using standardize cognitive assessment tools, such as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and global severity scales. Two of the most commonly used global severity scales are the Functional Assessment Staging (FAST) scale and the Clinical Dementia Rating (CDR) scale. The FAST scale measures functional status in dementia and consists of 7 major stages split into 16 different substages ( Table 41.2 ). The CDR rates impairments in memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care based on a semistructured interview with the patient and an informant. The CDR ranges from 0 to 3, with higher scores indicating a greater severity of impairment. Although no singular definition of advanced dementia exists, individuals generally must score 10 or less on the MMSE, meet criteria for stage 6 or 7 on the FAST, or score a 3 on the CDR ( Table 41.3 ).

Table 41.2
Summary of Functional Assessment Staging (FAST)
From Risberg B. Functional Assessment Staging (FAST). Psychopharmacol Bulletin . 1988;24(4):653–659.
Stage 1 No subjective or objective impairments in cognition
Stage 2 Mainly subjective complains of forgetting names and misplacing objects
Stage 3 Objective evidence of memory impairment, impairment beginning to affect work performance
Stage 4 Moderate cognitive decline, with impairments in instrumental activities of daily living
Stage 5 Difficulty with naming current aspects of life and some disorientation
Stage 6 (a–e) Difficulty dressing, bathing, toileting without assistance; later divisions include urinary (6d) and fecal (6e) incontinence
Stage 7 (a–f) Speech declines from <6 intelligible words per day (7a) to ≤1 (7b); progressive loss of ability to ambulate (7c), sit up (7d), smile (7e), and hold head up (7f)

Table 41.3
Staging the Severity of Dementia
ADL, activity of daily living; CDR, Clinical Dementia Rating; FAST, Functional Assessment Staging scale; IADL, instrumental activity of daily living; MMSE, Mini-Mental State Examination.
Severity or Stage Reference Examples of Deficits
Mild
  • MMSE>18

  • FAST stage 4

  • CDR=1

  • Difficulty with IADLs such as finances, shopping, medication management

  • May need prompting for personal care

Moderate
  • MMSE=10–18

  • FAST stages 5 and 6

  • CDR=2

  • Same as for mild, plus difficulties with simpler food preparation, household cleanup, and yard work; may require some assistance with some self-care

Severe
  • MMSE<10

  • FAST stages 6 and 7

  • CDR=3

  • Requires near total assistance with ADLs such as bathing, dressing, toileting, transferring

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