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.

Epidemiology
  • The global prevalence of dementia from all causes is estimated to be between 5% and 7% of adults over the age of 60.[1].
    • The incidence of dementia then doubles every 5 years after age 65.[2]
  • 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%).
  • Females with dementia outnumber males by 2 to 1
Prognosis

Normal Aging and Cognition

  • Decline in problem-solving, processing speed, and minor delays in word-finding can be common in normal ageing. Retrieval-type memory deficits are also commonly reported. In contrast to dementia, semantic memory and visuospatial functioning is generally preserved.

Prevention

About 35%-40% of dementia cases are attributable to 9 modifiable factors across the lifespan.[4] These factors include:[5]

  • 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)[6]
  • Diabetes
  • Physical inactivity
  • Smoking
  • Social isolation

More recently, the 2020 Lancet Commission on Dementia Prevention, Intervention and Care now include 12 potentially modifiable risk factors across the lifespan that can contribute to dementia:[7]

There remains debate as to how many cases of dementia with modifiable risk factors can truly be prevented even with risk factor modification.[8]

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:[9]
  1. Physical exercise (there is some conflicting data[10])
  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)

Diet

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.[11] Vitamins B and E, polyunsaturated fatty acids, and multivitamins are not recommended for risk reduction of dementia.[12][13]

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:[14]

  1. Rule out delirium. Is there an acute onset and fluctuating course + inattention + disorganized thinking? Is there altered level of consciousness?
    • Urinary tract infections are common in the elderly and can be causes of delirium! Additionally, a negative urine culture does not always mean there is no UTI, especially if the patient has classic symptoms of a UTI.[15] On the other hand, however, asymptomatic bacteriuria should not be treated with an antibiotic, due to adverse risks such as C. Diff infections and lack of evidence for changing outcomes.[16]
  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
    • Medication-induced “dementia”
      • Is there polypharmacy that could be contributing to the cognitive impairment?
      • Is there the use of any anticholinergic medications (and anticholinergic toxicity?)
      • Is there the use of other medications that could cause cognitive issues?
        • e.g. - steroid dementia syndrome related to glucocorticoid use.
    • Consider other neurological disorders including normal pressure hydrocephalus
  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).[17] 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
Dementia with Lewy Bodies (DLB) 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%[18] (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 [19] 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[20] 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[21] 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 Dementia with Lewy Bodies (DLB).[22]

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.

Dementia, Depression, or Delirium?

  • In the geriatric population, it is important to differentiate between delirium, dementia, and depression, which can be difficult to distinguish.[23][24][25] The prevalence of delirium superimposed on dementia ranges anywhere from 22% to 89% of hospitalized and community populations aged 65 and older with dementia.
  • The negative outcomes of these co-occurring conditions include accelerated and long-term cognitive, functional decline, institutionalization, re-hospitalization, and increased mortality.[26]

A Comparison of Delirium, Dementia, and Depression

Adapted from: Fong, T., et al. Delirium in elderly adults: diagnosis, prevention and treatment. Nature Reviews Neurology 5.4 (2009): 210.
Delirium Dementia Depression
Cardinal feature Confusion and Inattention Memory loss Sadness, anhedonia
Onset Acute or subacute Insidious Slow
Course Fluctuating, often worse at night Chronic, progressive (but stable over the course of a day) Single or recurrent episodes; can be chronic
Duration Hours to months Months to years Weeks to years
Level of Conciousness (LOC) Impaired, fluctuates Normal in early stages Normal
Attention (i.e. - able to focus on tasks) Poor Normal (except in
late stages) 		May be impaired
Orientation (i.e. - date, location) Fluctuates Poor Normal
Memory (i.e. - short-term memory) Poor Poor May be impaired
Hallucinations Common (visual) Rare, except in
late stages (and depends on type of dementia) 		Not usually (only if psychotic depression)
Delusions Fleeting, non-systematized Often absent Not usually (only if psychotic depression)
Psychomotor Increased (hyperactive) or reduced (hypoactive) No Yes
Reversibility Yes Rarely Yes
EEG Findings Moderate to severe background slowing Normal or mild diffuse slowing Normal (usually)

Neuroimaging

For older patients with cognitive symptoms, neuroimaging (MRI preferred over CT) is recommended if the following criteria is present:[27][28]

  • Onset of cognitive signs/symptoms within the past 2 years, regardless of the rate of progression
  • Unexpected and unexplained decline in cognition and/or functional status in a patient already known to have dementia
  • Recent and significant head trauma
  • Unexplained neurological manifestations (new onset severe headache, seizures, Babinski sign, etc.), at onset or during evolution (this also includes gait disturbances)
  • History of cancer, in particular if at risk for brain metastases
  • Risk for intracranial bleeding
  • Symptoms suggestive of normal pressure hydrocephalus
  • Significant vascular risk factors
  • Unusual or atypical cognitive symptoms or presentation (e.g. progressive aphasia)

Guidelines

Dementia Guidelines

Guideline Location Year PDF Website
Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) - Diagnosis and Treatment Canada 2020 - Link
CCCDTD - Pharmacological Recommendations for Symptomatic Treatment of Dementia Canada 2012 - Link
Deprescribing.org (Bruyère Research Institute) and University of Sydney Deprescribing Guidelines International 2018 - 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 Patients/Family
For Providers
Articles/News

References

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2) Corrada, M. M., Brookmeyer, R., Paganini‐Hill, A., Berlau, D., & Kawas, C. H. (2010). Dementia incidence continues to increase with age in the oldest old: the 90+ study. Annals of neurology, 67(1), 114-121.
3) Geschwind, M. D., Haman, A., & Miller, B. L. (2007). Rapidly progressive dementia. Neurologic clinics, 25(3), 783-807.
4) 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.
5) Steffens, D. C. (2018). A Geriatrics Perspective on Dementia Prevention and Treatment.
6) Byers, A. L., & Yaffe, K. (2011). Depression and risk of developing dementia. Nature Reviews Neurology, 7(6), 323.
7) Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Livingston, Gill et al. The Lancet
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9) World Health Organization. (2019). Risk reduction of cognitive decline and dementia: WHO guidelines. In Risk reduction of cognitive decline and dementia: WHO guidelines.
10) 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.
11) Ludwig, D. S., Ebbeling, C. B., & Heymsfield, S. B. (2019). Improving the quality of dietary research. Jama, 322(16), 1549-1550.
12) 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).
13) Rutjes, A. W., Denton, D. A., Di Nisio, M., Chong, L. Y., Abraham, R. P., Al‐Assaf, A. S., ... & McCleery, J. (2018). Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life. Cochrane database of systematic reviews, (12).
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15) 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.
16) Nicolle, L. E., Gupta, K., Bradley, S. F., Colgan, R., DeMuri, G. P., Drekonja, D., ... & Siemieniuk, R. (2019). Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 68(10), e83-e110.
17) Paterson, R. W., Takada, L. T., & Geschwind, M. D. (2012). Diagnosis and treatment of rapidly progressive dementias. Neurology: Clinical Practice, 2(3), 187-200.
18) 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.
19) 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.
20) Grossman, M. (2010). Primary progressive aphasia: clinicopathological correlations. Nature Reviews Neurology, 6(2), 88.
21) Agarwal, S., & Gilbert, R. (2018). Progressive Supranuclear Palsy. In StatPearls [Internet]. StatPearls Publishing.
22) 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.
23) Brown, T. M., & Boyle, M. F. (2002). Delirium. Bmj, 325(7365), 644-647.
24) Fong, T. G., Davis, D., Growdon, M. E., Albuquerque, A., & Inouye, S. K. (2015). The interface of delirium and dementia in older persons. The Lancet. Neurology, 14(8), 823.
25) Fong, T. G., Tulebaev, S. R., & Inouye, S. K. (2009). Delirium in elderly adults: diagnosis, prevention and treatment. Nature reviews neurology, 5(4), 210.
26) Fick, D. M., Agostini, J. V., & Inouye, S. K. (2002). Delirium superimposed on dementia: a systematic review. Journal of the American Geriatrics Society, 50(10), 1723-1732.
27) 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.
28) Ismail, Z., Black, S. E., Camicioli, R., Chertkow, H., Herrmann, N., Laforce Jr, R., ... & CCCDTD5 participants. (2020). Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia. Alzheimer's & Dementia, 16(8), 1182-1195.