MD Notes

creation date: 2026-02-12 16:33
tags: Pathologies

Dementia

Background

Definitions

Dementia is a progressive and persistent decline in cognition domains including executive function, complex attention, language, learning, memory, perceptual-motor, or social cognition, that results in a decline in the patient’s ability to function.

Dementia is also referred to as major neurocognitive disorder (MND) to remove the association with the elderly. It may be used interchangeably.

Subtype and Pathogenesis

The major subtypes of of dementia includes:

Alzheimer disease (70%)
The exact pathogenesis of Alzheimer disease is unclear but involves the overproduction and/or decreased clearance of amyloid beta pepetides. These amyloids are produced by the endoproteolytic cleavage of amyloid beta precursor protein.

A second protein tau, is also complicit in the pathogenesis. It become hyperphosphorylated and aggregates, becoming neurotoxic.

Generally, Alzheimer disease is a disease of older age with most cases occurring following the age of 65. Earlier onset is associated with atypical presentation.

The disease follows a insidious course, starting with a prodromal stage of mild cognitive impairment, before progressing into mild, moderate, and severe dementia.

Vascular dementia (10-20%)
Vascular dementia refers to dementia that is primarily caused by cerebrovascular disease or impaired cerebral blood flow. As such onset is often sudden following a incident such as a stroke.

In this case, the dementia is a syndrome of a disease that causes brain injury, for example, ischemic stroke. In many cases, pure vascular dementia is uncommon and often involves another etiology.

Frontotemporal dementia (10%)
FTD refers to a heterogeneous disorder characterized by disturbances in behaviour, personality, and language accompanied by focal neurodegeneration of the frontal and/or temporal lobes.

This is a highly heritable condition that involves degeneration of the lobes involving microvacuolation and neuronal loss accompanied by swollen neurons, loss of myelin, and astrocytic gliosis.

Several subtypes of FTD exist which vary in the composition of protein inclusions, their morphology, and anatomical distribution.

Dementia with Lewy bodies (4%)
Dementia with Lewy bodies is characterized by similar neurodegenerative diseases such as Alzheimer and Parkinson disease but with the presence of Lewy bodies throughout the neocortex, brainstem, and limbic structures.

Other subtypes (1-5%)
The DSM-5 describes 13 total subtypes which account for the remaining prevalence. These include:

  • Parkinson disease
  • HIV infection
  • Huntington disease
  • Prion disease
  • Substance and medication use
  • Traumatic brain injury
  • Comorbid conditions

Clinical Presentation

Signs & Symptoms

Presentation of Alzheimer disease includes:

  • Memory impairment (most common initial symptom) - anterograde long-term episodic amnesia
  • Impairment in executive function and judgement/problem solving
  • Impairment in other cognitive domains (usually later stage)
  • Neuropsychiatric symptoms (apathy, social disengagement, irritability)
  • Apraxia (unable to perform learned tasks)
  • Olfactory dysfunction
  • Sleep disturbances
  • Seizures
  • Motor signs

Behaviour disturbances commonly peak in the late afternoon or evening (“sundowning”).

Atypical symptoms may be present with other subtypes of dementia:

  • Vascular dementia: deficits may occur in stepwise declines
  • Frontotemporal dementia: behavioural changes including disinhibition, apathy, and speech difficulties
  • Lewy body dementia: well-formed visual hallucinations, REM sleep disorder, parkinsonian symptoms, and fluctuating cognition, attention, and alertness

History & Physical Exam

History will likely be obtained from a combination of the patient and their family members, friends, or caregivers. The observed symptoms of cognitive decline and the severity of their impact should be defined.

It is important to evaluate their ability to perform daily tasks including:

  • Driving and driving safety
  • Episodes of getting lost
  • Ability to navigate house fires
  • Ability to communicate (eg. using the telephone)
  • Vulnerability to financial or physical abuse

A comprehensive physical exam may be required for parkinsonian syndromes. A neurological exam including gait analysis should be conducted.

Diagnosis

Criteria

The diagnosis of dementia depends on the subtype.

Alzheimer disease
The 2011 National Institute on Aging and the Alzheimer’s Association (NIA-AA) describes the criteria for a probable diagnosis:

  • Presence of dementia
  • Interference of work/usual activities
  • Not explained by delirium or major psychiatric disorder; no evidence of other subtypes of dementia
  • Cognitive impairment established by history from patient and a knowledgeable informant and objective bedside MSE/neuropsychologic testing
  • Cognitive impairment involving at least two of the following:
    • Impaired ability to acquire and remember new information
    • Impaired reasoning and handling of complex tasks, poor judgement
    • Impaired visuospatial abilities
    • Impaired language functions
    • Change in personality, behaviour, or comportment
  • Insidious onset and clear worsening/progression

The definitive diagnosis of Alzheimer disease requires histopathologic examination which is rarely done.

A diagnosis of mild cognitive impairment (MCI) may occur prior to full diagnosis. The NIA-AA criteria include:

  • A concern regarding cognition reported by the patient or informant or observed by the clinician
  • Objective evidence of impairment in one or more cognitive domains that is not explained by age or education
  • Preservation of independence in functional abilities
  • Impairments do not meet criteria for dementia

Vascular dementia
Dementia syndrome with evidence that cerebrovascular disease explains the cognitive deficits.

Frontotemporal dementia
Progressive deterioration in behaviour and/or cognition with early behavioural/personality change or dysfunction of executive functions

Dementia with Lewy bodies
Dementia syndrome with characteristic cognitive profile (attention, executive, visuoperceptual) rather than early memory loss.

Work-up

Initial evaluation
A number of standardized assessments can be used to document the presence and progression of dementia. Options include:

  • Montreal Cognitive Assessment (MoCA) - cut off for normal: 26, adjust based on education and other norms
  • Mini-Mental State Examination (MMSE)

Formal neuropsychological testing may be helpful and more sensitive to to impairments.

Neuroimaging
Brain MRI is indicated for evaluating patients with suspected Alzheimer disease. This serves to:

  • Rule out alternative diagnoses including cerebrovascular disease, structural diseases, or regional brain atrophy suggesting frontotemporal dementia
  • Detect structural findings consistent with Alzheimer (reduced hippocampal volume, medial temporal lobe atrophy)

Biomarkers
Several biomarkers can be used to support a diagnosis. The presence of amyloid is important for management.

  • Low CSF Aβ42
  • Positive amyloid PET imaging

Assessment of severity
For the purpose of treatment, establishing the severity of dementia can be made using MMSE, MoCA, or CDR scores.

  • Mild cognitive impairment: MMSE >23; CDR 0.5; evidence of cognitive decline but no loss of instrumental activities of daily living (ADLs)
  • Mild dementia: MMSE 19-26; MoCA 12-16; CDR 1; impairment in ≥1 instrumental ADLs
  • Moderate dementia: MMSE 10-18; MoCA 4-11; CDR 2; impairment in ≥1 ADLs
  • Severe dementia: MMSE <10; MoCA <4; CDR 3; impairment in most ADLs

Differential

The differential contains the various subtypes of dementia. Additionally it is important to distinguish between delirium and major depression prior to diagnosis.

Red Flags / Complications

Dementia is irreversible and as such complications primarily involve issues surrounding impaired cognition (eg. driving risks, wandering).

In cases of vascular dementia, recurrent stroke or cardiac conditions may increase mortality and as such appropriate management of risk factors should be done.

Management

Dementia care often involves specialists and multidisciplinary teams. This typically consist of specialty clinics.

Non-Pharmacological Therapy and Other Considerations

Nutrition
Weight changes in either direction may occur. Inadequate nutrition is more common due to poor appetite or decreased ability to self-care. Less commonly, excessive weight gain may occur due to disinhibition.

Initial steps to improve nutrition includes:

  • Environmental modification such as relaxed, home-style settings
  • Increasing flavour content and/or increasing textures

Subsequent interventions include assisted feeding and oral nutritional supplements.

Rehabilitation
Rehabilitation consist of improvement of quality of life. Components include:

  • Ensuring social interaction (even if passive participant)
  • Exercise programs
  • Occupational therapy

Alcohol limitation
Alcohol can exacerbate cognitive dysfunction and behavioural disturbances. Dementia may also cause patient to drink to excess due to losing track of drinks consumed.

In addition to limiting regular consumption, alcohol should be avoided following dinner due to its effect on sleep.

Capacity
Due to the cognitive compromising nature of dementia, patients may have reduced capacity. This encompasses medical, financial, and advance care decision-making.

Recommendations include:

  • Execution of a power of attorney (immediately or when further impairment is demonstrated)
  • Appointment of a health care proxy
  • Discussion of wishes for care (living at home, assisted living, nursing home)

Caregiver support
Dementia care can cause significant stress for caregivers. It is recommended to counsel caregivers regarding mental health as well as providing dementia care education.

Safety considerations
Driving cessation can be challenging and often represents a severe loss of independence. In Ontario, reporting is mandatory.

Patients are also at higher risk of:

  • Falls (consider gait assessment and physical therapy consultation)
  • Behavioural disturbances
  • Wandering and becoming loss
  • Risks associated with home safety (eg. cooking)

Disease-Specific Treatment

Alzheimer disease

For patients with dementia, treatment for symptom control consist of:

  • Cholinesterase inhibitors (eg. donepezil, rivastigmine, galantamine) - increases synaptic cholingeric transmission which may improve cognition and global functioning
  • Memantine - NMDA receptor antagonist, decreases glutamate action on cortical and hippocampal neurons which may reduce damage (thus preserving learning and memory)

As the above medications are for symptom control, they should be discontinued if the patient does not appear to be benefiting or if they have significant side effects.

Amyloid-targeted therapies are also available for reducing amyloid plaque burden. This is potentially disease modifying but requires weighing benefits to adverse effects.

  • Lecanemab or donanemab

Vascular dementia

The treatment for vascular dementia includes the symptom control components of Alzheimer management (cholinesterase inhibitors and memantine).

Additionally, vascular risk factors should be screened for and addressed to prevent recurrent stroke and further cerebrovascular disease.

  • Antihypertensive management (note: unclear evidence for target; reduce risk factor vs. compromised cerebral perfusion)
  • Diabetes management
  • Secondary prevention using statins and antiplatelet therapy

Frontotermporal dementia

Unlike Alzheimer, FTD is not associated with cholinergic system dysfunction and thus does not follow a similar treatment algorithm.

Primary considerations consist of medications for treatment of behavioural changes and depends on the spectrum of symptoms to manage. This typically involves SSRIs or antipsychotics.

Dementia with Lewy bodies

Treatment of DLB includes a trial cholinesterase inhibitors. The evidence for use of memantine is unclear as it has been noted to worsen hallucinations.

Due to the limited efficacy/poor tolerance of medications with DLB, nonpharmacological management remains the focus of treatment.

Specific pharmacotherapy may be indicated for specific symptoms (eg. Parkinsonian symptoms through Parkinson disease management).

Behavioural and Psychological Symptom Management

Screening for neuropsychiatric symptoms should be done regularly as they may be under-reported. Questions for the caregivers include:

  • Does the patient have any behaviours that worry you?
  • Does the patient have hallucinations, see things, or hear voices that aren’t there?
  • Home does the patient sleep at night?

With any new-onset behavioural abnormality, it is important to consider underlying causes such as new infection or medication toxicity. Adequate assessment and treatment should precede pharmacotherapy.

Agitation or aggression
Underlying conditions may include:

  • Medication side effects (especially anticholinergic medications)
  • Pain (agitation may be a manifestation of an inability to communicate pain)
  • Delirium
  • Depression (may not be verbalized - consider SSRI for initial therapy)
  • Sleep disorders
  • Misunderstanding/misperception due to poor vision or hearing
  • Delusions

Nonpharmacological approaches include:

  • Avoiding environmental triggers
  • Structured routines and calm reassurance

In severe or refractory cases, antipsychotics (olanzapine, quetiapine, pimavanserin) can be trialed. Treatment should only continue if benefits are apparent and discontinuation should be attempted regularly.

Depression
Diagnosis of depression in a patient with dementia or impaired cognition can be complicated.

Generally, treatment consist of SSRIs (note: TCAs have anticholingeric activity and should be avoided):

  • Sertraline
  • Citalopram

Apathy
Apathy is generally managed with cholinesterase inhibitors. This should be initiated if not already.

If apathy persist and is distressing, trial of an antidepressant and methylphenidate should be attempted (eg. citalopram + methylphenidate)

Sleep disorders
Sleep disturbances should be approached with nonpharmacologic strategies initially. This may include:

  • Implementing activity/exercise
  • Increasing natural light exposure during mornings
  • Limiting evening beverages and eliminating evening alcohol/coffee
  • Environmental restructuring (darkness, reduce noise, avoid nocturnal waking)

Pharmacotherapy should be avoided due to side effects.

Wandering
Wandering and becoming lost has the potential for physical harm or even death. If this is a leading concern, the patient may need to explore nursing home options.

Sexually inappropriate behaviour
There is little data on efficacy of medications for treatment of sexually inappropriate behaviour. Generally, behavioural interventions (eg. redirection, distraction) are attempted first. If insufficient, medications are trialed empirically for efficacy. Options include:

  • Antidepressants (usually first attempt)
  • Antipsychotics
  • Cholinesterase inhibitors
  • Gabapentin, pindolol, cimetidine
  • Hormonal agents

References

Tools / Guidelines

Additional Reading

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