Dementia: Difference between revisions

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A number of [[systematic review]]s, including ones by the [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)]<ref name="pmid12779304">{{cite journal |author=Boustani, M.; Peterson, B.; Hanson, L.; Harris, R.; & Lohr, K. |title=Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force |journal=Ann Intern Med |volume=138 |issue=11 |pages=927-37 |year=2003 |pmid=12779304 | url=http://www.annals.org/cgi/content/full/138/11/927}}</ref>, [http://jama.jamanetwork.com/collection.aspx?categoryid=6257 Rational Clinical Examination]<ref name="pmid17551132">{{cite journal |author=Holsinger T, Deveau J, Boustani M, Williams JW |title=Does this patient have dementia? |journal=JAMA |volume=297 |issue=21 |pages=2391–404 |year=2007 |pmid=17551132 |doi=10.1001/jama.297.21.2391}}</ref>, and others<ref name="pmid17178826">{{cite journal |author=Cullen B, O'Neill B, Evans JJ, Coen RF, Lawlor BA |title=A review of screening tests for cognitive impairment |journal=J. Neurol. Neurosurg. Psychiatr. |volume=78 |issue=8 |pages=790–9 |year=2007 |pmid=17178826 |doi=10.1136/jnnp.2006.095414}}</ref>, have summarized the diagnostic accuracy of screening tests.
A number of [[systematic review]]s, including ones by the [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)]<ref name="pmid12779304">{{cite journal |author=Boustani, M.; Peterson, B.; Hanson, L.; Harris, R.; & Lohr, K. |title=Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force |journal=Ann Intern Med |volume=138 |issue=11 |pages=927-37 |year=2003 |pmid=12779304 | url=http://www.annals.org/cgi/content/full/138/11/927}}</ref>, [http://jama.jamanetwork.com/collection.aspx?categoryid=6257 Rational Clinical Examination]<ref name="pmid17551132">{{cite journal |author=Holsinger T, Deveau J, Boustani M, Williams JW |title=Does this patient have dementia? |journal=JAMA |volume=297 |issue=21 |pages=2391–404 |year=2007 |pmid=17551132 |doi=10.1001/jama.297.21.2391}}</ref>, and others<ref name="pmid17178826">{{cite journal |author=Cullen B, O'Neill B, Evans JJ, Coen RF, Lawlor BA |title=A review of screening tests for cognitive impairment |journal=J. Neurol. Neurosurg. Psychiatr. |volume=78 |issue=8 |pages=790–9 |year=2007 |pmid=17178826 |doi=10.1136/jnnp.2006.095414}}</ref>, have summarized the diagnostic accuracy of screening tests.
<ref name="pmid14981170">{{cite journal| author=Canning SJ, Leach L, Stuss D, Ngo L, Black SE| title=Diagnostic utility of abbreviated fluency measures in Alzheimer disease and vascular dementia. | journal=Neurology | year= 2004 | volume= 62 | issue= 4 | pages= 556-62 | pmid=14981170 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14981170  }} </ref>
One minute screening tests, such as the inability to name 15 or more animals in one minute, predicts the presence of dementia.<ref name="pmid14981170">{{cite journal| author=Canning SJ, Leach L, Stuss D, Ngo L, Black SE| title=Diagnostic utility of abbreviated fluency measures in Alzheimer disease and vascular dementia. | journal=Neurology | year= 2004 | volume= 62 | issue= 4 | pages= 556-62 | pmid=14981170 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14981170  }} </ref>


The single best finding may be disoriented to year.<ref name="pmid20852313">{{cite journal| author=O'Keeffe E, Mukhtar O, O'Keeffe ST| title=Orientation to time as a guide to the presence and severity of cognitive impairment in older hospital patients. | journal=J Neurol Neurosurg Psychiatry | year= 2011 | volume= 82 | issue= 5 | pages= 500-4 | pmid=20852313 | doi=10.1136/jnnp.2010.214817 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20852313  }} </ref>
The single best finding may be disoriented to year.<ref name="pmid20852313">{{cite journal| author=O'Keeffe E, Mukhtar O, O'Keeffe ST| title=Orientation to time as a guide to the presence and severity of cognitive impairment in older hospital patients. | journal=J Neurol Neurosurg Psychiatry | year= 2011 | volume= 82 | issue= 5 | pages= 500-4 | pmid=20852313 | doi=10.1136/jnnp.2010.214817 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20852313  }} </ref>

Revision as of 20:04, 1 May 2016

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Dementia is "progressive decline in two or more cognitive domains that is severe enough to interfere with the performance of everyday activities."[1]

Deficits in cognitive function contribute to impaired functional status.[2] The deficits in the domains of cognitive function are[3]:

  • Agnosia - "Failure to recognize or identify objects despite intact sensory function"[3]
  • Aphasia - "Deterioration of language function"[3]
  • Apraxia - "Impaired ability to execute motor activities despite intact motor abilities, sensory function, and comprehension of the required task"[3]
  • Disturbance in executive functioning - "The ability to think abstractly and to plan, initiate, sequence, monitor, and stop complex behavior"[3]

Classification

Vascular dementia can affect both cortical and subcortial locations.

Cortical dementias

Among the many causes of cortical dementia, common causes are:

Subcortical dementias

Among the many causes of subcortical dementia, common causes are:

Epidemiology

22.2% of individuals in the United States age 71 years or older have cognitive impairment without dementia (Dementia Severity Rating Scale score of 6 to 11). 12% of these patients progress to dementia annually. Progression is more common among patients with subtypes of prodromal Alzheimer disease and cerebrovascular disease.[5]

Risk factors

Repeated episodes of hypoglycemia are associated with dementia.[6]

Hypoxia from sleep disordered breathing such as sleep apnea may increase risk.[7]

Diagnosis

Studies on diagnosing dementia are compromised by the lack of a true reference standard for comparison.[8][9]

A number of systematic reviews, including ones by the U.S. Preventive Services Task Force (USPSTF)[10], Rational Clinical Examination[3], and others[11], have summarized the diagnostic accuracy of screening tests.

[12]

One minute screening tests, such as the inability to name 15 or more animals in one minute, predicts the presence of dementia.[12]

The single best finding may be disoriented to year.[13]

Ascertainment of decision making capacity

Decision making can be assessed with the Aid to Capacity Evaluation (ACE).[14]

Consequences of labeling

In one study, learning of having mild cognitive impairment reduced stress.[15]

Mental status schedules

Systematic reviews have compared the schedules.[16][3]

A separate systematic review has examined decision making capacity.[14]

Temporal disorientation

Among hospitalized geriatric patients, "failure to identify either year or month correctly was 95% sensitive and 86.5% specific for the detection of cognitive impairment".[13]

Diagnostic surveys have been compared.[17]

Sweet 16

The Sweet 16 is available online at http://hospitalelderlifeprogram.org/private/sweet16-disclaimer.php?pageid=01.09.00. Accuracy using a score of less than 14:[18]

Mini-cog

According to the systematic review by the Rational Clinical Examination, regarding the mini-cog "the performance of the Mini-Cog...cannot be determined with confidence because none of these screens were actually administered in their suggested forms. However, the performance suggested by the retrospective analyses reported in these articles is promising."[3] More recent studies[19] and reviews[20] are favorable. The mini-COG is available at http://www.hospitalmedicine.org/geriresource/toolbox/pdfs/clock_drawing_test.pdf and http://geriatrics.uthscsa.edu/tools/MINICog.pdf .

Mini-mental state examination

The Mini-mental state examination (MMSE) is the most studied test.[3] A systematic review concluded that the accuracy of the MMSE is:[10]:

Copies of their MMSE can be purchased (http://www4.parinc.com/Products/Product.aspx?ProductID=MMSE). A copy of the Mini-mental state examination can be found in the appendix of the original publication.[21]

Modified Mini-Mental State examination (3MS)

A meta-analysis concluded that the Modified Mini-Mental State (3MS) examination has:[11]

A copy of the 3MS is online.[22]

Abbreviated mental test score

A meta-analysis concluded:[11]

sensitivity 73% to 100%
specificity 71% to 100%

Clinical Dementia Rating

The Clinical Dementia Rating scale can quantify severity of functional impairment.[23]

Clock drawing task

Dementia type CLOX1
(Executive control) 		CLOX2
(Posterior cortical) 		Pentagons copying
on MMSE 		Total MMSE score
Posterior cortical and
diffuse cortical
dementias 		Abnormal Abnormal Abnormal Abnormal
Subcortical and
frontal cortical
dementias 		Abnormal Normal Normal Normal

The Clock drawing task (CLOX) consists of two tests and is available online at PubMed Central.[24] The CLOX1 task has the subject draw a clock face without any prompting other than the instructions "Draw me a clock that says 1:45. Set the hands and numbers on the face so that a child could read them". The CLOX1 is tests executive function and correlates with the EXIT25 test of executive function. The CLOX2 task has the subject copy a clock face from an example, does not test executive function and correlates with the MMSE.

The CLOX may avoid the bias of the MMSE toward cortical dementias.[24] In addition, "as Alzheimer's disease affects posterior cortical regions before invading the frontal cortex, isolated ECF impairment (CLOX1) is not likely to represent early Alzheimer's disease."[24] Thus, isolated abnormalities of the CLOX1 may be able to detect reversible dementias such as subcortical stroke, depression, vitamin B12 deficiency, polypharmacy, and hypothyroidism.[24]

Saint Louis University mental status examination (SLUMS)

The SLUMS has been compared to the MMSE.[25][26] Both evaluations were by the developer of the SLUMS and showed comparable accuracy to the MMSE.

Other examinations

Many other tests have been studied [27][28][1] including the Executive Interview (EXIT)[29].[30]

Investigation of causes

Among rapidly progressive cases, causes include:[31]

  • Sporadic Creutzfeldt-Jakob disease (sCJD)
  • Immunological (vasculitis, encephalomyelitis, and limbic encephalitis)
  • Neoplastic (mainly lymphoma)
  • Infectious (fungal, viral, and parasitic)
  • Metabolic (including Wernicke encephalopathy)

Laboratory tests

Apolipoprotein E4

Although apolipoprotein E4 is an important susceptibility gene for Alzheimer's disease[32], its sensitivity and specificity are insufficient (65 and 68 percent, respectively) to be used as a diagnostic test.[33]

Apolipoprotein E4 does not added to other tests in predicting who will develop Alzheimer's.[34]

Treatment

Approaches to treatment

"Actively involving caregivers in making choices about treatments" my be the most important way to delay institutionalization of patients with dementia.[35]

The use of care managers may help.[36][37]

Non drug treatments

Behavior management techniques (BMT)

Behavior management techniques (BMT) might help.[38] More specifically, " interventions that address behavioral issues and unmet needs" may help.[36]

Exercise

Home-based program of physical activity might benefit according to a randomized controlled trial.[39]

Bright lights

Any initial randomized controlled trial suggests that bright light helps.[40]

Medications

According to the clinical practice guideline by the American College of Physicians, "the evidence is insufficient to compare the effectiveness of different pharmacologic agents for the treatment of dementia."[41]

"Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia" according to a systematic review for the clinical practice guideline.[42]

Cholinesterase inhibitors

Available cholinesterase inhibitors drugs are donepezil, galantamine, rivastigmine, and tacrine.

Neuropeptide-modifier

Memantine is a neuropeptide-modifier that acts on the N-Methyl-D-Aspartate (NMDA) cell surface receptors for the neurotransmitter glutamate.

Anti-psychotics

The newer, atypical antipsychotic agents (olanzapine, quetiapine, risperidone), were found to have "adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease."[43] A more recent randomized controlled trial that compared the second generation anti-psychotic agents found that none improved functioning, care needs, or quality of life with statistical significance[43]; however, olanzapine and risperidone may reduce anger.[44] Regardless, antipsychotic agents may increase mortality.[45]

Withdrawing psychotropics agents may prevent accidental falls.[46]

Melatonin

Melatonin may[47]or may not[48][49][50][51] help with associated sleep and behavior disturbance.

Dietary supplements

Ginkgo biloba has conflicting evidence regarding its efficacy.[52][53][54]

Randomized controlled trials of B vitamins[55] [56] [57] [58]
Trial Patients Intervention Comparison Outcome Results Comment
Intervention Control
Ford[55]
2010		 • ≥ 75 years old, with hypertension but without dementia or depression
• No restrictions on folic acid, vitamin B12, and homocysteine levels		 • 2 mg/d of folate
• 25 mg/d of vitamin B6
• 400 microg/d of vitamin B12		 Placebo Tests of cognition     negative study, but positive trend
Aisen[56]
2008		 • Mild to moderate Alzheimers disease
• Normal folic acid, vitamin B12, and homocysteine levels		 • 5 mg/d of folate
• 25 mg/d of vitamin B6
• 1 mg/d of vitamin B12		 Placebo Tests of cognition     negative study
Durga[57]
2007		 50-70 years old
• raised plasma homocysteine
• normal serum vitamin B12		 800 microg/d folate Placebo Tests of cognition     A secondary publication of a study of folate originally for effect on carotid intimal thickness. In the current study, 3 of 6 measures of cognitive function improved. This publication contains an evidence table that summarizes prior studies.
McMahon[58]
2006		 ≥ 65 years old
• raised plasma homocysteine		 • 1000 microg/d folate
• 500 microg/d of Vitamin B12
• 10 mg/d of vitamin B6		 Placebo Tests of cognition     negative study

Analgesics

Treating pain may reduce agitation.[59]

Prevention

Physical activity

Most,[60][61][62][63] but not all[64] studies find that physical activity is associated with reduced risk of dementia. These observational studies cannot prove cause and effect.

Mental activity

"Exergaming" may help.[65]

Maintaining activities such as cognitive games and reading, playing musical instruments, and physical activities are associated with reduced the risk of dementia in an observational study.[64]

Medications

Various medications have been associated with progression or prevention (cholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, renin-angiotensin system blockers, and hydroxymethylglutaryl-coenzyme A reductase inhibitors) of dementia.[66]

Observational, non-ramdomized cohort studies suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) may[67][68] or may not[69][70] prevent dementia.

Supplements

Ginkgo biloba does not prevent dementia according to a large randomized controlled trial[71] and systematic review[54] by the Cochrane Collaboration in spite of earlier studies that were positive[72].

Screening

Practice guidelines

In 2003, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) gave a grade I recommendation, indicating "the evidence is insufficient to recommend for or against routine screening for dementia in older adults".[73]

Evidence

The late-life dementia risk index:[74]

late-life dementia risk index
Risk Score Incidence of dementia
within 6 years
High ≥8 56%
Intermediate 4-7 23%
Low 0-3 4%
Based on Table 3 from Barnes et al.[74]
  • older age (1–2 points)
  • poor cognitive test performance (2–4 points)
  • body mass index <18.5 (2 points)
  • ≥1 apolipoprotein E 4 alleles (1 point)
  • cerebral MRI findings of white matter disease (1 point)
  • cerebral ventricular enlargement (1 point)
  • internal carotid artery thickening on ultrasonography (1 point)
  • history of coronary artery bypass surgery (1 point)
  • slow physical performance (1 point)
  • lack of alcohol consumption (1 point)

Prognosis

Functional Assessment Staging (FAST) scale[75]
Stage 6
6a = inability to dress
6b = inability to bathe
6c = inability to toilet
6d = urinary incontinence at least occasionally
6e = bowel incontinence at least occasionally
Stage 7
7a = speech is limited to less than 5 words
7b = all intelligible vocabulary is lost
7c = nonambulatory
7d = unable to sit independently
7e = unable to smile
7f = unable to hold head up

Mild cognitive impairment

Mortality is increased with mild cognitive impairment.[76] A systematic review of cohort studies concluded that the rate conversion of mild cognitive impairment to dementia is about 4% per year."[77]

Once a patient has advanced dementia, defined as a score of 5 or 6 on the Cognitive Performance Scale from the most recent Minimum Data Set assessment (a score of 5 corresponds to a score of 5.1 (95% CI: ±10) on the Folstein Mini–Mental State Examination, the median survival is about 18 months.[78]

Dementia

Mortality can also be predicted by Medicare guidelines for use of Hospice. If the patients is a stage 7c on the Functional Assessment Staging (FAST) scale and has had a prior complication of dementia such aspiration pneumonia, stage 4 or more pressure ulcer, upper urinary tract infection, or inability to eat, then mortality is predicted at 6 months with accuracy of:[79]

  • Sensitivity 20%
  • Specificity 89%

Similarly, mortality can be predicted by the ADEPT score.[79]

References

  1. ↑ 1.0 1.1 Karlawish, J. & Clark, C. (2003). "Diagnostic evaluation of elderly patients with mild memory problems". Ann Intern Med 138 (5): 411-9. PMID 12614094.
  2. ↑ Royall DR, Lauterbach EC, Kaufer D, Malloy P, Coburn KL, Black KJ (2007). "The cognitive correlates of functional status: a review from the Committee on Research of the American Neuropsychiatric Association". The Journal of neuropsychiatry and clinical neurosciences 19 (3): 249–65. DOI:10.1176/appi.neuropsych.19.3.249. PMID 17827410. Research Blogging.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Holsinger T, Deveau J, Boustani M, Williams JW (2007). "Does this patient have dementia?". JAMA 297 (21): 2391–404. DOI:10.1001/jama.297.21.2391. PMID 17551132. Research Blogging. Cite error: Invalid <ref> tag; name "pmid17551132" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid17551132" defined multiple times with different content
  4. ↑ McKeith IG, Fairbairn AF, Perry RH, Thompson P (September 1994). "The clinical diagnosis and misdiagnosis of senile dementia of Lewy body type (SDLT)". Br J Psychiatry 165 (3): 324–32. PMID 7994501. [e]
  5. ↑ Plassman BL, Langa KM, Fisher GG, et al (March 2008). "Prevalence of cognitive impairment without dementia in the United States". Ann. Intern. Med. 148 (6): 427–34. PMID 18347351. [e]
  6. ↑ Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP, Selby JV (April 2009). "Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus". JAMA 301 (15): 1565–72. DOI:10.1001/jama.2009.460. PMID 19366776. Research Blogging.
  7. ↑ Yaffe, Kristine; Alison M. Laffan, Stephanie Litwack Harrison, Susan Redline, Adam P. Spira, Kristine E. Ensrud, Sonia Ancoli-Israel, Katie L. Stone (2011). "Sleep-Disordered Breathing, Hypoxia, and Risk of Mild Cognitive Impairment and Dementia in Older Women". JAMA: The Journal of the American Medical Association 306 (6): 613 -619. DOI:10.1001/jama.2011.1115. Retrieved on 2011-08-11. Research Blogging.
  8. ↑ Erkinjuntti T, Ostbye T, Steenhuis R, Hachinski V (December 1997). "The effect of different diagnostic criteria on the prevalence of dementia". N. Engl. J. Med. 337 (23): 1667–74. PMID 9385127. [e]
  9. ↑ Rockwood K et al. Toward a revision of criteria for the dementias. Alzheimer's and Dementia 3 (4), 428 (2007) DOI:10.1016/j.jalz.2007.07.014
  10. ↑ 10.0 10.1 Boustani, M.; Peterson, B.; Hanson, L.; Harris, R.; & Lohr, K. (2003). "Screening for dementia in primary care: a summary of the evidence for the U.S. Preventive Services Task Force". Ann Intern Med 138 (11): 927-37. PMID 12779304.
  11. ↑ 11.0 11.1 11.2 Cullen B, O'Neill B, Evans JJ, Coen RF, Lawlor BA (2007). "A review of screening tests for cognitive impairment". J. Neurol. Neurosurg. Psychiatr. 78 (8): 790–9. DOI:10.1136/jnnp.2006.095414. PMID 17178826. Research Blogging.
  12. ↑ 12.0 12.1 Canning SJ, Leach L, Stuss D, Ngo L, Black SE (2004). "Diagnostic utility of abbreviated fluency measures in Alzheimer disease and vascular dementia.". Neurology 62 (4): 556-62. PMID 14981170. [e]
  13. ↑ 13.0 13.1 O'Keeffe E, Mukhtar O, O'Keeffe ST (2011). "Orientation to time as a guide to the presence and severity of cognitive impairment in older hospital patients.". J Neurol Neurosurg Psychiatry 82 (5): 500-4. DOI:10.1136/jnnp.2010.214817. PMID 20852313. Research Blogging.
  14. ↑ 14.0 14.1 Sessums LL, Zembrzuska H, Jackson JL (2011). "Does this patient have medical decision-making capacity?". JAMA 306 (4): 420-7. DOI:10.1001/jama.2011.1023. PMID 21791691. Research Blogging. Cite error: Invalid <ref> tag; name "pmid21791691" defined multiple times with different content
  15. ↑ Carpenter, B. D., Xiong, C., Porensky, E. K., Lee, M. M., Brown, P. J., Coats, M., et al. (2008). Reaction to a dementia diagnosis in individuals with Alzheimer's disease and mild cognitive impairment, Journal of the American Geriatrics Society, 56(3), 405-412. DOI:doi:10.1111/j.1532-5415.2007.01600.x. doi:10.1111/j.1532-5415.2007.01600.x.
  16. ↑ Lin JS, O'Connor E, Rossom RC, Perdue LA, Eckstrom E (2013). "Screening for cognitive impairment in older adults: A systematic review for the U.S. Preventive Services Task Force.". Ann Intern Med 159 (9): 601-12. DOI:10.7326/0003-4819-159-9-201311050-00730. PMID 24145578. Research Blogging. Review in: Ann Intern Med. 2014 Feb 18;160(4):JC12
  17. ↑ Holsinger T, Plassman BL, Stechuchak KM, Burke JR, Coffman CJ, Williams JW (2012). "Screening for cognitive impairment: comparing the performance of four instruments in primary care.". J Am Geriatr Soc 60 (6): 1027-36. DOI:10.1111/j.1532-5415.2012.03967.x. PMID 22646750. Research Blogging.
  18. ↑ Fong TG, Jones RN, Rudolph JL, Yang FM, Tommet D, Habtemariam D et al. (2011). "Development and validation of a brief cognitive assessment tool: the sweet 16.". Arch Intern Med 171 (5): 432-7. DOI:10.1001/archinternmed.2010.423. PMID 21059967. Research Blogging.
  19. ↑ Hirsch C (2012). "The Mini-Cog had sensitivity similar to the longer 3MS for detecting cognitive impairment or dementia.". Ann Intern Med 157 (8): JC4-8. DOI:10.7326/0003-4819-157-8-201210160-02008. PMID 23070510. Research Blogging.
  20. ↑ Mitchell AJ, Malladi S (2010). "Screening and case finding tools for the detection of dementia. Part I: evidence-based meta-analysis of multidomain tests.". Am J Geriatr Psychiatry 18 (9): 759-82. DOI:10.1097/JGP.0b013e3181cdecb8. PMID 20808118. Research Blogging.
  21. ↑ Folstein MF, Folstein SE, McHugh PR (1975). ""Mini-mental state". A practical method for grading the cognitive state of patients for the clinician". Journal of psychiatric research 12 (3): 189-98. DOI:10.1016/0022-3956(75)90026-6. PMID 1202204. Research Blogging.
  22. ↑ Hogan DB, Ebly EM (2000). "Predicting who will develop dementia in a cohort of Canadian seniors". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 27 (1): 18–24. PMID 10676583. [e] [Appendix: The Modified Mini-Mental State (3MS)]
  23. ↑ Morris JC (1993). "The Clinical Dementia Rating (CDR): current version and scoring rules.". Neurology 43 (11): 2412-4. PMID 8232972.
  24. ↑ 24.0 24.1 24.2 24.3 Royall, D.; Cordes J.; & Polk M. (1998). "CLOX: an executive clock drawing task". J Neurol Neurosurg Psychiatry 64 (5): 588-94. PMID 9598672. Full text at PubMed Central Example form
  25. ↑ Cummings-Vaughn LA, Chavakula NN, Malmstrom TK, Tumosa N, Morley JE, Cruz-Oliver DM (2014). "Veterans affairs saint louis university mental status examination compared with the montreal cognitive assessment and the short test of mental status.". J Am Geriatr Soc 62 (7): 1341-6. DOI:10.1111/jgs.12874. PMID 24916485. Research Blogging.
  26. ↑ Tariq SH, Tumosa N, Chibnall JT, Perry MH, Morley JE (2006). "Comparison of the Saint Louis University mental status examination and the mini-mental state examination for detecting dementia and mild neurocognitive disorder--a pilot study.". Am J Geriatr Psychiatry 14 (11): 900-10. DOI:10.1097/01.JGP.0000221510.33817.86. PMID 17068312. Research Blogging.
  27. ↑ Sager, M.; Hermann, B.; La Rue, A.; & Woodard, J. (2006). "Screening for dementia in community-based memory clinics". WMJ 105 (7): 25-9. PMID 17163083.
  28. ↑ Fleisher, A.; Sowell B.; Taylor C.; Gamst A.; Petersen R.; & Thal L. (2007). "Clinical predictors of progression to Alzheimer's disease in amnestic mild cognitive impairment". Neurology 68 (19): 1588-95. PMID 17287448.
  29. ↑ Royall DR, Mahurin RK, Gray KF. Bedside assessment of executive cognitive impairment: the executive interview. J Am Geriatr Soc. 1992;40:1221-6. PMID 1447438
  30. ↑ Carpenter CR, Bassett ER, Fischer GM, Shirshekan J, Galvin JE, Morris JC (2011). "Four sensitive screening tools to detect cognitive dysfunction in geriatric emergency department patients: brief Alzheimer's Screen, Short Blessed Test, Ottawa 3DY, and the caregiver-completed AD8.". Acad Emerg Med 18 (4): 374-84. DOI:10.1111/j.1553-2712.2011.01040.x. PMID 21496140. PMC PMC3080244. Research Blogging.
  31. ↑ Chitravas N, Jung RS, Kofskey DM, Blevins JE, Gambetti P, Leigh RJ et al. (2011). "Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease.". Ann Neurol. DOI:10.1002/ana.22454. PMID 21674591. Research Blogging.
  32. ↑ Skoog I (August 2000). "Detection of preclinical Alzheimer's disease". N. Engl. J. Med. 343 (7): 502–3. PMID 10944568. “The APOE 4 allele is a susceptibility gene for Alzheimer's disease and seems to affect the age of onset of the disease. However, the presence of this allele alone is not sufficient to predict which asymptomatic subjects will ultimately have Alzheimer's disease, and the disease never develops in many subjects with this genotype” [e]
  33. ↑ Kivipelto M, Helkala EL, Laakso MP, et al (August 2002). "Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer's disease". Ann. Intern. Med. 137 (3): 149–55. PMID 12160362. [e]
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