Key Clinical Updates in Dementia
Aducanumab was approved by the FDA despite mixed results in clinical trials. Its use is limited to patients with mild cognitive impairment or mild dementia and amyloid pathology proven by amyloid PET. The ultimate role of this medication is still being debated.
ESSENTIALS OF DIAGNOSIS
Progressive intellectual decline.
Not due to delirium or psychiatric disease.
Age is the main risk factor, followed by family history and vascular disease risk factors.
Dementia is a progressive decline in intellectual function that is severe enough to compromise social or occupational functioning. Mild cognitive impairment describes a decline that has not resulted in a change in the level of function. Although a few patients identify a precipitating event, most experience an insidious onset and gradual progression of symptoms.
Dementia typically begins after age 60, and the prevalence doubles approximately every 5 years thereafter; in persons aged 85 and older, around half have dementia. The prevalence of Alzheimer dementia is predicted to be 15 million by 2060 in the United States. In most cases, the cause of dementia is acquired, either as a sporadic primary neurodegenerative disease or as the result of another disorder, such as stroke (Table 24–6). Other risk factors for dementia include family history, diabetes mellitus, cigarette smoking, hypertension, obesity, a history of significant head injury, and hearing loss. Vitamin D deficiency and chronic sleep deprivation may also increase the risk of dementia. Dementia is more prevalent among women, but this may be accounted for by their longer life expectancy. Physical activity seems to be protective; education, ongoing intellectual stimulation, and social engagement may also be protective, perhaps by promoting cognitive reserve, an improved capacity to compensate for insidious neurodegeneration.
Table 24–6.Common causes of age-related dementia (listed by prevalence). ||Download (.pdf) Table 24–6. Common causes of age-related dementia (listed by prevalence).
|Plaques containing beta-amyloid peptide, and neurofibrillary tangles containing tau protein, occur throughout the neocortex.
Most common age-related neurodegenerative disease; incidence doubles every 5 years after age 60.
Short-term memory impairment is early and prominent in most cases.
Variable deficits of executive function, visuospatial function, and language.
|Multifocal ischemic change.
|Dementia with Lewy bodies
|Histologically indistinguishable from Parkinson disease: alpha-synuclein-containing Lewy bodies occur in the brainstem, midbrain, olfactory bulb, and neocortex. Alzheimer pathology may coexist.
Cognitive dysfunction, with prominent visuospatial and executive deficits.
Psychiatric disturbance, with anxiety, visual hallucinations, and fluctuating delirium.
Parkinsonian motor deficits with or after other features.
Cholinesterase inhibitors lessen delirium; poor tolerance of neuroleptics and dopaminergics.
|Frontotemporal dementia (FTD)
|Neuropathology is variable and defined by the protein found in intraneuronal aggregates. Tau protein, TAR DNA-binding protein 43 (TDP-43), or fused-in-sarcoma (FUS) protein account for most ...