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://www.sgim.org/clinexam-rce.cfm 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://www.sgim.org/clinexam-rce.cfm 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.
===Ascertainment of decision making capacity===
Decision making can be assessed with the  [http://crashingpatient.com/wp-content/pdf/ACE.pdf Aid to Capacity  Evaluation] (ACE).<ref name="pmid21791691">{{cite journal|  author=Sessums LL, Zembrzuska H, Jackson JL| title=Does this patient  have medical decision-making capacity? | journal=JAMA | year= 2011 |  volume= 306 | issue= 4 | pages= 420-7 | pmid=21791691 |  doi=10.1001/jama.2011.1023 | pmc= |  url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21791691  }} </ref>


===Consequences of labeling===
===Consequences of labeling===

Revision as of 19:21, 12 September 2011

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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.

Ascertainment of decision making capacity

Decision making can be assessed with the Aid to Capacity Evaluation (ACE).[12]

Consequences of labeling

In one study, learning of having mild cognitive impairment reduced stress.[13]

Investigation of causes

Among rapidly progressive cases, causes include:[14]

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

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".[15]

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:[16]

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 ther 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.[17]

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.[18]

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.[19]

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.[20] 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.[20] 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."[20] Thus, isolated abnormalities of the CLOX1 may be able to detect reversible dementias such as subcortical stroke, depression, vitamin B12 deficiency, polypharmacy, and hypothyroidism.[20]

Other examinations

Many other tests have been studied [21][22][1] including the Executive Interview (EXIT)[23].

Laboratory tests

Apolipoprotein E4

Although apolipoprotein E4 is an important susceptibility gene for Alzheimer's disease[24], its sensitivity and specificity are insufficient (65 and 68 percent, respectively) to be used as a diagnostic test.[25]

Apolipoprotein E4 does not added to other tests in predicting who will develop Alzheimer's.[26]

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.[27]

The use of care managers may help.[28][29]

Non drug treatments

Behavior management techniques (BMT)

Behavior management techniques (BMT) might help.[30] More specifically, " interventions that address behavioral issues and unmet needs" may help.[28]

Exercise

Home-based program of physical activity might benefit according to a randomized controlled trial.[31]

Bright lights

Any initial randomized controlled trial suggests that bright light helps.[32]

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."[33]

"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.[34]

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."[35] 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[35]; however, olanzapine and risperidone may reduce anger.[36] Regardless, antipsychotic agents may increase mortality.[37]

Withdrawing psychotropics agents may prevent accidental falls.[38]

Melatonin

Melatonin may[39]or may not[40][41][42][43] help with associated sleep and behavior disturbance.

Dietary supplements

Ginkgo biloba has conflicting evidence regarding its efficacy.[44][45][46]

Analgesics

Treating pain may reduce agitation.[47]

Prevention

Physical activity

Most[48][49][50][51], but not all[52] studies find that physical activity is associated with reduced risk of dementia. These observational studies cannot prove cause and effect.

Mental activity

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.[52]

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.[53]

Observational, non-ramdomized cohort studies suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) may[54][55] or may not[56][57] prevent dementia.

Supplements

Ginkgo biloba does not prevent dementia according to a large randomized controlled trial[58] and systematic review[46] by the Cochrane Collaboration in spite of earlier studies that were positive[59].

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".[60]

Evidence

The late-life dementia risk index:[61]

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.[61]
  • 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[62]
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

A systematic review of cohort studies concluded that the rate conversion of mild cognitive impairment to dementia is about 4% per year."[63]

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.[64]

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:[65]

  • Sensitivity 20%
  • Specificity 89%

Similarly, mortality can be predicted by the ADEPT score.[65]

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 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.
  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. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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)]
  19. ↑ Morris JC (1993). "The Clinical Dementia Rating (CDR): current version and scoring rules.". Neurology 43 (11): 2412-4. PMID 8232972.
  20. ↑ 20.0 20.1 20.2 20.3 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
  21. ↑ 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.
  22. ↑ Fleisher, A.; Sowell B.; Taylor C.; Gamst A.; Petersen R.; & Thal L. (2007). "Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment". Neurology 68 (19): 1588-95. PMID 17287448.
  23. ↑ 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
  24. ↑ 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]
  25. ↑ 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 disease". Ann. Intern. Med. 137 (3): 149–55. PMID 12160362. [e]
  26. ↑ Devanand DP, Liu X, Tabert MH, et al (November 2008). "Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease". Biol. Psychiatry 64 (10): 871–9. DOI:10.1016/j.biopsych.2008.06.020. PMID 18723162. Research Blogging.
  27. ↑ Spijker A et al. Effectiveness of Nonpharmacological Interventions in Delaying the Institutionalization of Patients with Dementia: A Meta-Analysis.J Am Geriatr Soc. 2008 Apr 11. PMID 18410323
  28. ↑ 28.0 28.1 Ayalon L, Gum AM, Feliciano L, Areán PA (2006). "Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review". Arch. Intern. Med. 166 (20): 2182–8. DOI:10.1001/archinte.166.20.2182. PMID 17101935. Research Blogging.
  29. ↑ Vickrey BG, Mittman BS, Connor KI, et al (2006). "The effect of a disease management intervention on quality and outcomes of dementia care: a randomized, controlled trial". Ann. Intern. Med. 145 (10): 713–26. PMID 17116916. [e]
  30. ↑ Teri L, Gibbons LE, McCurry SM, et al (2003). "Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial". JAMA 290 (15): 2015–22. DOI:10.1001/jama.290.15.2015. PMID 14559955. Research Blogging.
  31. ↑ Lautenschlager NT, Cox KL, Flicker L, Foster JK, van Bockxmeer FM, Xiao J, et al. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial. JAMA. 2008 Sep 3;300(9):1027-1037.
  32. ↑ Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ (June 2008). "Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial". JAMA 299 (22): 2642–55. DOI:10.1001/jama.299.22.2642. PMID 18544724. Research Blogging.
  33. ↑ Qaseem A, Snow V, Cross JT, et al (March 2008). "Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians". Ann. Intern. Med. 148 (5): 370–8. PMID 18316755. [e]
  34. ↑ Raina P, Santaguida P, Ismaila A, et al (March 2008). "Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline". Ann. Intern. Med. 148 (5): 379–97. PMID 18316756. [e]
  35. ↑ 35.0 35.1 Schneider LS, Tariot PN, Dagerman KS, et al (2006). "Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease". N. Engl. J. Med. 355 (15): 1525–38. DOI:10.1056/NEJMoa061240. PMID 17035647. Research Blogging. Cite error: Invalid <ref> tag; name "pmid17035647" defined multiple times with different content
  36. ↑ Sultzer DL, Davis SM, Tariot PN, Dagerman KS, Lebowitz BD, Lyketsos CG et al. (2008). "Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial.". Am J Psychiatry 165 (7): 844-54. DOI:10.1176/appi.ajp.2008.07111779. PMID 18519523. PMC PMC2714365. Research Blogging. Review in: Evid Based Ment Health. 2009 Feb;12(1):20
  37. ↑ Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K et al. (2009). "The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial.". Lancet Neurol 8 (2): 151-7. DOI:10.1016/S1474-4422(08)70295-3. PMID 19138567. Research Blogging. Review in: Ann Intern Med. 2009 Jun 16;150(12):JC6-8 Review in: Evid Based Med. 2009 Aug;14(4):115
  38. ↑ Campbell AJ, Robertson MC, Gardner MM, Norton RN, Buchner DM (1999). "Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial". J Am Geriatr Soc 47 (7): 850–3. PMID 10404930. [e]
  39. ↑ Dowling GA, Burr RL, Van Someren EJ, Hubbard EM, Luxenberg JS, Mastick J et al. (2008). "Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer's disease.". J Am Geriatr Soc 56 (2): 239-46. DOI:10.1111/j.1532-5415.2007.01543.x. PMID 18070004. PMC PMC2642966. Research Blogging.
  40. ↑ Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2009). "Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease.". Am J Geriatr Psychiatry 17 (2): 166-9. DOI:10.1097/JGP.0b013e318187de18. PMID 19155748. PMC PMC2630117. Research Blogging.
  41. ↑ Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M et al. (2003). "A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease.". Sleep 26 (7): 893-901. PMID 14655926.
  42. ↑ Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P (2002). "Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia.". Int J Geriatr Psychiatry 17 (12): 1120-7. DOI:10.1002/gps.760. PMID 12461760. Research Blogging.
  43. ↑ Haffmans PM, Sival RC, Lucius SA, Cats Q, van Gelder L (2001). "Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.". Int J Geriatr Psychiatry 16 (1): 106-10. PMID 11180494.
  44. ↑ Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R (2002). "Ginkgo for memory enhancement: a randomized controlled trial". JAMA 288 (7): 835–40. PMID 12186600. [e]
  45. ↑ Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF (1997). "A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group". JAMA 278 (16): 1327–32. PMID 9343463. [e]
  46. ↑ 46.0 46.1 Birks J, Grimley Evans J (2009). "Ginkgo biloba for cognitive impairment and dementia". Cochrane Database Syst Rev (1): CD003120. DOI:10.1002/14651858.CD003120.pub3. PMID 19160216. Research Blogging.
  47. ↑ Husebo BS, Ballard C, Sandvik R, Nilsen OB, Aarsland D (2011). "Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial.". BMJ 343: d4065. DOI:10.1136/bmj.d4065. PMID 21765198. Research Blogging.
  48. ↑ Byles JE, Sanson-Fisher RW (June 1996). "Mass mailing campaigns to promote screening for cervical cancer: do they work, and do they continue to work?". Aust N Z J Public Health 20 (3): 254–60. PMID 8768414. [e]
  49. ↑ Ravaglia G, Forti P, Lucicesare A, et al (2007). "Physical activity and dementia risk in the elderly. Findings from a prospective Italian study". Neurology. DOI:10.1212/01.wnl.0000296276.50595.86. PMID 18094335. Research Blogging.
  50. ↑ Larson EB, Wang L, Bowen JD, et al (2006). "Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older". Ann. Intern. Med. 144 (2): 73–81. PMID 16418406. [e]
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