Introduction to Dementia

Primer

Dementia is a syndrome characterized by progressive neurocognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities. It is a broad diagnostic category that includes Alzheimer's disease, Lewy Body dementia, frontotemporal dementia, vascular dementia, Parkinson's disease, and Creutzfeldt–Jakob disease (among many others). It also includes rapidly progressive dementias that may be fully reversible if the etiology is correctly identified.

Prevalence

The global prevalence of dementia from all causes is estimated to be between 5% and 7% of adults over the age of 60.[1]. Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and dementia rates start at 5-10% at age 70. By age 85, between 25% and 50% of people will exhibit signs of Alzheimer's disease. The percentage of all dementias due to Alzheimer's disease is at least 50% (with some estimates suggesting 60-90%).

Aging and Cognition

With normal aging, semantic memory and visuospatial functioning is generally preserved. Decline in problem-solving, processing speed, and minor delays in word-finding can be common. Retrieval-type memory deficits can also occur.

Prevention

About 35%-40% of dementia cases are attributable to nine modifiable factors across the lifespan.[2] These factors include: education, midlife hypertension, midlife obesity, hearing loss, late-life depression (note: depression likely has a bidirectional relationship with dementia risk, as it can be both a risk factor for dementia and a prodrome of dementia), diabetes, physical inactivity, smoking, and social isolation.[3]

More recently, the 2020 Lancet Commission on Dementia Prevention, Intervention and Care updated the risk factors to now include 12 potentially modifiable risk factors across the lifespan that can contribute to dementia: early life (education), midlife (hypertension, obesity, hearing loss, traumatic brain injury, and alcohol misuse) and later life (smoking, depression, physical inactivity, social isolation, diabetes, and air pollution).[4] There is some debate as to how many of these cases with modifiable risk factors can truly be prevented even with risk factor modification.[5]

Dietary supplementation to prevent dementia has been a source of controversy due to a lack of convincing evidence from current studies, low quality studies, and multiple confounders in dietary research.[6] Vitamins B and E, polyunsaturated fatty acids, and multivitamins are not recommended for risk reduction of dementia.[7]

The World Health Organization (WHO) Dementia Prevention Guidelines

The World Health Organization (WHO) Dementia Prevention Guidelines recommends the following to reduce the risk of dementia:[8]
  1. Physical exercise (there is some conflicting data[9])
  2. Tobacco cessation
  3. Reduce harmful drinking
  4. Lose excess weight in midlife
  5. Adhere to healthy diet (a Mediterranean-style diet may reduce dementia risk)
  6. Cognitive training can be tried for adults with normal cognition or mild impairment (but the quality of evidence to support this is low)
  7. Social participation and support are important throughout life (but limited evidence to support)
  8. Hypertension, diabetes, and depression should be managed according to existing guidelines (but it is not clear whether doing so will specifically lower dementia risk)

Approach to Dementia

When seeing a patient with a non-rapidly progressive dementia (otherwise, see the rapidly progressive dementia approach below), it is good to have a systematic approach. The following is one approach:[10]

  1. Rule out delirium. Is there an acute onset and fluctuating course + inattention + disorganized thinking? Is there altered level of consciousness?
    • Urinary Tract Infections (UTIs) are especially common in the elderly and frequent culprits of delirium! Don't forget that a negative urine culture does not always mean there is no UTI, especially if the patient is symptomatic.[11]
  2. Rule out depression (“pseudodementia”). Consider atypical presentations: anxiety, irritability, unexplained physical complaints, worsening cognition. Once the depression is treated, the dementia symptoms go away!
  3. Rule out any substance use disorders
  4. Rule out any reversible causes
    • Order CBC (anemia), TSH (hypothyroidism), creatinine, electrolytes (hyponatremia), calcium (hypercalcemia), glucose (hyperglycemia), ferritin/iron, and vitamin B12 (vitamin B12 deficiency)
    • Creatinine (to assess renal function and ability to clear medications)
    • Consider neuroimaging such as CT or MRI
    • Consider screening for syphillis
    • Is there the use of any anticholinergic medications (and anticholinergic toxicity?)
  5. Is it dementia, mild cognitive impairment (MCI), or normal aging?

Rapidly Progressive Dementias

Rapidly Progressive Dementias (RPDs) are dementias that progress quickly – over the course of weeks to months (in rarer cases, may be over a period of 1-2 years).[12] Treatment of an RPD is dependent on the etiology of the dementia, some of which are fully treatable. This makes early recognition critical. Broadly, RPDs can be broken down into different etiologies:

  1. Prion disease (e.g. - Creutzfeldt-Jakob Disease (CJD))
  2. Neurodegenerative diseases (e.g. - early onset Alzheimer's Disease (AD))
  3. Autoimmune
  4. Infectious
  5. Psychiatric
  6. Neoplastic
  7. Toxic-Metabolic
  8. Vascular
  9. Leukoencephalopathies (e.g. - Multiple Sclerosis (MS), Progressive Multifocal Leukoencephalopathy)

Mnemonic

Evaluating for RPDs requires a detailed and systematic approach, and a mnemonic can be useful to do this. The mnemonic VITAMINS can be used to remember the

  • V - Vascular
  • I - Infectious
  • T - Toxic-Metabolic
  • A - Autoimmune
  • M - Metastasis/Neoplastic
  • I - Iatrogenic
  • N - Neurodegenerative
  • S - Systemic/Seizures

Common Dementias

The most common dementia subtypes are below:

Common Dementia Subtypes and Presentation

Subtype Percent of Dementia Cases Typical presentation
Alzheimer's Disease (AD) ~50% Initial short-term memory loss
Vascular Dementia* ~25% Vascular risk factors; neuroimaging evidence of cerebrovascular involvement
Lewy Body Dementia (LBD) 15% Bradykinesia or features of parkinsonism, fluctuating cognition, visual hallucinations
Frontotemporal Dementia (FTD) 3% Younger age, behavioural symptoms, or language impairment
Parkinsons's Disease Dementia (PDD) 0.5%[13] (most cases of Parkinson's will progress to dementia) Dementia occurring > 1 year after onset of Parkinson disease motor symptoms
*Includes mixed dementia types (Vascular and Alzheimer's). Mixed types become more common in later–life dementia.

Rare Dementias

Rarer dementia subtypes include the following:

Rare Dementia Subtypes and Presentation

Subtype Prevalence Typical presentation
Corticobasal Degeneration (CBD) 5 per 100,000 [14] Progressive asymmetric movement disorder with symptoms initially affecting one limb, plus cognitive or behavioural disturbances.
Creutzfeldt-Jakob Disease (CJD) 1 per 1 million Rapid, progressive mental deterioration with myoclonus and abnormal movements. Survival rate is less than 1 year.
Primary Progressive Aphasia (PPA) 2.7 to 15 per 100,000[15] Begins with gradual, subtle language deficits that progresses to a nearly complete inability to speak.
Progressive Supranuclear Palsy (PSP) 5.8 to 6.5 per 100,000[16] Characterized by early postural instability, leading to falls, and a characteristic vertical supranuclear-gaze palsy on physical exam.

Mixed Presentations

Dementia is often due to more than one pathology. Some studies have shown that in a general population, 40% of patients have a combination of Alzheimer's Disease (AD) and vascular dementia, while only 30% had pure Alzheimer's and 12% had pure vascular dementia (VaD). About 12% had Alzheimer's combined with Parkinsons's Disease Dementia (PDD) (PD) or Lewy Body Dementia (LBD).[17]

Behavioural and Psychological Symptoms of Dementia

Behavioural and Psychological Symptoms of Dementia (BPSD) will develop in more than 90% of individuals diagnosed with dementia. Symptoms include delusions, hallucinations, aggression, screaming, restlessness, wandering, depression, and anxiety.

Neuroimaging

For older patients with cognitive symptoms, neuroimaging with CT is recommended if the following criteria is present:[18]

  • Age less than 60 years
  • Rapid (e.g., 1 or 2 months) unexplained decline in cognition or function
  • “Short” duration of dementia (less than 2 years)
  • Recent and signicant head trauma
  • Unexplained neurological symptoms (e.g. new onset of severe headache or seizures)
  • History of cancer (especially in sites and types that metastasize to the brain)
  • Use of anticoagulants (i.e. - history of atrial fibrillation) or history of bleeding disorder
  • History of urinary incontinence and gait disorder early in the course of dementia (as may be found in normal pressure hydrocephalus)
  • Any new localizing sign (e.g., hemiparesis or a Babinski reflex)
  • Unusual or atypical cognitive symptoms or presentation (e.g. progressive aphasia)
  • Gait disturbance

Guidelines

Dementia Guidelines

Guideline Location Year PDF Website
Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) Canada 2020 - Link
National Institute for Health and Care Excellence (NICE) UK 2018 - Link
American Psychiatric Association (APA) USA 2007, 2014 - • Guideline (2007)
• Guideline Watch (2014)
• Quick Reference

Resources

For Providers
For Patients/Family
Articles/News

References

1) Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., & Ferri, C. P. (2013). The global prevalence of dementia: a systematic review and metaanalysis. Alzheimer's & dementia, 9(1), 63-75.
2) Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J., Ames, D., ... & Cooper, C. (2017). Dementia prevention, intervention, and care. The Lancet, 390(10113), 2673-2734.
3) Steffens, D. C. (2018). A Geriatrics Perspective on Dementia Prevention and Treatment.
4) Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Livingston, Gill et al. The Lancet
5) Montero-Odasso, M., Ismail, Z., & Livingston, G. (2020). One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case “for” and “against”. Alzheimer's Research & Therapy, 12(1), 1-5.
6) Ludwig, D. S., Ebbeling, C. B., & Heymsfield, S. B. (2019). Improving the quality of dietary research. Jama, 322(16), 1549-1550.
7) McCleery, J., Abraham, R. P., Denton, D. A., Rutjes, A. W., Chong, L. Y., Al‐Assaf, A. S., ... & Di Nisio, M. (2018). Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment. Cochrane Database of Systematic Reviews, (11).
8) World Health Organization. (2019). Risk reduction of cognitive decline and dementia: WHO guidelines. In Risk reduction of cognitive decline and dementia: WHO guidelines.
9) Kivimäki, M., Singh-Manoux, A., Pentti, J., Sabia, S., Nyberg, S. T., Alfredsson, L., ... & Kouvonen, A. (2019). Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis. bmj, 365, l1495.
10) Lee, L., Weston, W. W., Heckman, G., Gagnon, M., Lee, F. J., & Sloka, S. (2013). Structured approach to patients with memory difficulties in family practice. Canadian Family Physician, 59(3), 249-254.
11) Heytens, S., De Sutter, A., Coorevits, L., Cools, P., Boelens, J., Van Simaey, L., ... & Claeys, G. (2017). Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases. Clinical Microbiology and Infection, 23(9), 647-652.
12) Paterson, R. W., Takada, L. T., & Geschwind, M. D. (2012). Diagnosis and treatment of rapidly progressive dementias. Neurology: Clinical Practice, 2(3), 187-200.
13) Aarsland, D., Zaccai, J., & Brayne, C. (2005). A systematic review of prevalence studies of dementia in Parkinson's disease. Movement disorders: official journal of the Movement Disorder Society, 20(10), 1255-1263.
14) Bergeron, C., Pollanen, M. S., Weyer, L., Black, S. E., & Lang, A. E. (1996). Unusual clinical presentations of cortical‐basal ganglionic degeneration. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 40(6), 893-900.
15) Grossman, M. (2010). Primary progressive aphasia: clinicopathological correlations. Nature Reviews Neurology, 6(2), 88.
16) Agarwal, S., & Gilbert, R. (2018). Progressive Supranuclear Palsy. In StatPearls [Internet]. StatPearls Publishing.
17) Sonnen, J. A., Larson, E. B., Crane, P. K., Haneuse, S., Li, G., Schellenberg, G. D., ... & Montine, T. J. (2007). Pathological correlates of dementia in a longitudinal, population‐based sample of aging. Annals of neurology, 62(4), 406-413.
18) Gauthier, Serge et al. “Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4)” Canadian geriatrics journal : CGJ vol. 15,4 (2012): 120-6.