Dementia

Dementia, relabelled major neurocognitive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is a clinical syndrome defined by progressive decline in one or more cognitive domains relative to a person's premorbid functional level. To fulfill the criteria for dementia, the resulting cognitive impairment must significantly interfere with independence in performing activities of daily living ^1,2.

Terminology

The use of dementia in the literature is heterogeneous with varying definitions ⁸. Some authors include both reversible and irreversible causes of cognitive impairment in their definition of dementia, whilst others state that dementia is irreversible ⁶ and that conditions with reversible causes should not be classified as dementia. Thus, depending on the definition, chronic subdural hematoma and normal pressure hydrocephalus may or may not be included as causes of dementia.

Given this heterogeneity, it is prudent to use the word dementia increasingly sparingly ¹⁰ and probably err on the side of reserving it for the subgroup of conditions that everyone agrees are on the list: irreversible neurodegenerative disease (e.g. Alzheimer disease, frontotemporal lobar degeneration, etc).

Young-onset dementia, also known as early-onset dementia and historically as presenile dementia, is a term that can be defined as dementia onset before 65 years (range 60-70 years) ⁷.

Epidemiology

Alzheimer's disease accounts for ~70% (range 60-80%) of all dementias, with an increased prevalence in older adults ^3,4. The innumerable other causes of dementia listed below have various risk factors discussed in their dedicated articles.

Clinical presentation

Dementia is considered an acquired illness caused by a disease process affecting the brain, though this process may be a result of congenital or acquired factors.

Each cause of dementia presents with a different constellation of impaired cognitive domains, with the potential for associated neurologic findings depending on the pathophysiology. There is considerable overlap between the resulting clinical syndromes, especially in late disease and in older comorbid patients who may have multiple causes contributing to the presenting dementia syndrome.

The broad cognitive domains that may be affected in dementia include ¹:

• complex attention

• executive function

• learning and memory

• language

• perceptual-motor function

• social cognition and behavior

Pathology

Etiology

• neurodegenerative disease

  • Alzheimer disease

  • vascular dementia

  • limbic-predominant age-related TDP-43 encephalopathy (LATE)

  • dementia with Lewy bodies

  • Parkinson disease dementia

  • frontotemporal lobar degeneration

    • behavioral variant frontotemporal dementia

    • primary progressive aphasia

    • corticobasal degeneration

  • progressive supranuclear palsy

  • multiple system atrophy

  • cerebral amyloid angiopathy

  • chronic traumatic encephalopathy

  • Huntington disease

  • prion diseases e.g. Creutzfeldt-Jakob disease

• other central nervous system pathology that is not strictly neurodegenerative and may be reversible

  • chronic subdural hematoma

  • normal pressure hydrocephalus

  • brain tumor

• chronic use of psychoactive substances

  • alcohol

  • sedatives, hypnotics or anxiolytics

  • other substances e.g. volatile inhalants

• autoimmune disorders

  • multiple sclerosis

  • cerebral vasculitis

  • systemic lupus erythematosus

• infection

  • HIV-associated dementia

  • herpes simplex encephalitis

  • progressive multifocal leukoencephalopathy

• endocrine

  • hypothyroidism

  • hyperparathyroidism

• electrolyte derangement

  • hyper or hyponatremia

  • hyper or hypocalcemia

  • hypokalemia

  • hypercupremia e.g. Wilson disease

• other serum abnormalities

  • hyperammonemia

  • uremia

• micronutrient deficiencies including thiamine, B6, B12, folate

• medication effects and interactions

• toxin exposure e.g. heavy metals

Radiographic features

Refer to each specific article for detailed discussion of the radiographic features of the different causes of dementia.

Differential diagnosis

Dementia must be distinguished clinically from other entities that may present with cognitive impairment, including:

• delirium

  • more acute onset, featuring fluctuating deficits of attention and consciousness

• pseudodementias

  • depression is most common, but other psychiatric conditions (e.g. mania, psychosis, conversion disorder, and malingering) can mimic depression ⁵

  • may have memory or concentration deficits

  • negative symptoms e.g. apathy lead to poor effort during psychological evaluation, compared to patients with true dementia who apply great effort but produce incorrect answers

  • psychomotor retardation or agitation may also feature

  • pseudodementia and dementia can coexist

• normal aging-associated cognitive decline

  • commonly presents with memory deficits that are mild/subclinical, not progressive and not impacting on functional independence

• mild neurocognitive disorder

  • cognitive decline greater than is attributable to normal aging, but not meeting DSM-5 criteria for dementia because functional independence is preserved ^1,2

• intellectual disability

• neurodevelopmental disorder

• current substance intoxication or withdrawal

See also

• causes of dementia (mnemonic)