Contents

Search

mild cognitive impairment (MCI); benign senile forgetfulness; age-associated memory impairment (AAMI)

Questionable dementia or possible Alzheimer's disease (AD). MCI corresponds to a clinical dementia rating (CDR) of 0.5. Classification: 1) amnestic: memory impairment 2) nonamnestic: memory intact - cognitive impairment in other domain [2] Etiology: - higher medical burden increases risk for MCI [46] - COPD increases risk for MCI - RR for non-amnestic MCI is 1.86 [14] - chronic hypertension - SPRINT group reports reduction in mild cognitive impairment, but not dementia using SPRINT goals* (14.6 vs 18.3 per 1000 person-years) [36] - treatment reduces risk 20.2% vs 21.1% within 4 years [41] - diabetes mellitus may increase risk & may accelerate progression of MCI to dementia [2,40] - frailty increases risk [43] - parasympatholytics increase risk [44] - ApoE4 positivity [46] * systolic BP < 120 mm Hg Epidemiology: - 13% of adults > 60 years of age report memory problems or confusion during preceding year [13] - 6.7% age 60-64 years, 25.2% age 80-84 years [31] Pathology: 1) some neuropathologic data support the view that MCI is early Alzheimer's disease (AD) 2) late-life cognitive impairment generally results from a combination of vascular & neurofibrillary pathology 3) most patients with MCI have mixed AD pathology - concurrent cerebrovascular disease in 60-70% [27] - < 25% with pure AD pathology [27] Clinical manifestations: 1) mild dysfunction from age-related cognitive impairment - activities of daily living intact (basic & instrumental) - driving is not an activity of daily living [6] 2) 6-12 month history of worsening memory complaints - difficulty remembering recent conversations [50] - difficulty remembering appointments [50] 3) retrieval difficulty that improves with recognition & cueing 4) disproportionate declines in visuospatial memory 5) difficulty with working memory 6) decline in other cognitive domains may occur in the absence of memory impairment, i.e. verbal fluency & visuospatial deficits [2] 7) MCI can occur across multiple domains, including executive function 8) difficulty managing money may be an early sign of cognitive impairment in the elderly [45] 9) functional impairment not severe enough to require help with activities of daily living (ADL) 10) psychological well-being may decline prior to onset of MCI [54] - purpose in life & personal growth most notable declines 11) positive relationships with others decline after diagnosis of MCI [54] Laboratory: - dementia workup maybe appropriate (see dementia) - CSF for beta-amyloid & tau & apoE4 genotype with some predictive value for progression to Alzheimer's disease [8] - tau in CSF + amyloid-beta 42 in CSF in addition to brain MRI proposed to predict progression of mild cognitive impairment to Alzheimer's disease [28] - decline in function better predictor than biomarkers [8] - tau in CSF & amyloid-beta 42 in CSF best biomarkers [22] * no clinical markers or diagnostic tests can predict the likelihood of progression to dementia [6] Special laboratory: - evidence of cognitive impairment on cognitive testing [6] - difficulty in recall of 3 items [50] - difficulty drawing intersecting pentagons [50] - neuropsychologic testing may be helpful a) combination of 4 office-based tests with 80% predictive value for progression to dementia [4] b) mood disorder (depression or anxiety) may predict progression to dementia [5] c) delayed verbal memory along with MRI findings are best predictors of progression to Alzheimer's disease [8] - insufficient evident to support routine cognitive testing in elderly with MCI [6] * prediction model for conversion of normal cognition to MCI [33,42] - baseline age & education - neuropsychological assessment - Digit Symbol Substitution Test - from the Wechsler Adult Intelligence Scale - Revised & the Verbal Paired Associates - Immediate recall from the Wechsler Memory Scale - phosphorylated tau in CSF & amyloid-beta in CSF - right hippocampal volume & right entorhinal cortex thickness measurements from brain MRI - apoE genotype [33] Radiology: - neuroimaging indicated to exclude structural lesions [6] - MRI: thickness of left middle temporal lobe cortex predicts progression to Alzheimer's disease [8] - positron emission tomography (PET scan) - FDG-PET scan [22] - amyloid PET: both amyloid-positive & amyloid-negative results associated with changes in diagnosis & treatment - not routinely indicated [6] Complications: - annual conversion rate to Alzheimer's disease is 5-15% [6,9]* - 15% conversion to dementia in 4.5 years [23] - 15% conversion to dementia within 2 years in patients > 65 years [31] - reversion to normal cognition uncommon [9] - people with MCI & the apoE4 allele progress to Alzheimer's disease more rapidly - multidomain MCI, antidepressant use, & depressive symptoms associated with clinical progression to dementia [46] - vulnerability to scams in older patients is associated with cognitive impairment & Alzheimer dementia [37] * ref [21] gives very different estimates Differential diagnosis: 1) age-associated memory impairment - no significant functional impairment 2) early dementia a) greater severity of memory difficulty b) greater problems responding to memory cues c) needs assistance with activities of daily living (bADL or iADL) Management: 1) no effective pharmacotherapy to prevent MCI or slow transition to dementia [6] - no indication for cholinesterase inhibitors to prevent or treat MCI [6] - oral Chinese herbal medicine plus donepezil appears more effective than donepezil alone in improving the cognitive function of MCI* [55] - SSRI may delay onset on dementia in depressed patients with MCI [30] (for up to 3 years) - vitamin D 400 IU/day may slow progression of MCI [14] - vitamin D supplementation of no benefit [52] - omega-3 fatty acid of no benefit [2] - improved glycemic control may slow progression to dementia in patients with diabetes mellitus [2,40] - aducanumab-avwa (Aduhelm) FDA approved using accelerated approval pathway 2) discontinue anticholinergic agents & benzodiazepines, if possible 3) nicotine patch may have benefit(s), but editorialist advises against use [10] 4) cognitive rehabilitation somewhat effective in some patients [6,12] 5) ensure adequate nutrition 6) exercise of benefit [19,29] 7) aerobic exercise of benefit [20] - improves executive control processes for older women at high risk of cognitive decline - improves executive functioning in elderly with MCI [35] - also see exercise for seniors 8) memory training programs - no evidence that games or puzzles designed to stimulate memory will affect cognitive ability. (GRS11) [2] - computerized cognitive training - studies yield conflicting results - computerized drill & practice & virtual-reality interventions with some effect that quickly diminish when activity discontinued [24] - cognitive training may be of some benefit [32] 9) aerobic-resistance exercises with sequential computerized cognitive training may improve cognition [52] - magnitude of benefit is small [52] 10) consistent engagement in mentally stimulating activities may reduce risk for MCI in late life [25] - apoE4 allele may attenuate this MCI risk reduction [25] 11) multidomain interventions (combined cognitive & physical training for < 1 year) associated with improvements in global cognition, memory, executive function, & verbal fluency vs single interventions in older adults with MCI [48] 12) older adults with MCI were more likely to regain normal cognition if they engaged in positive thinking about aging [49] 13) caution patients about driving 14) control of cardiovascular risk factors may slow progression to Alzheimer's disease 15) requires no further evaluation [6] 16) quality measures [38] - annual cognitive health assessment for patients >= 65 years - cognitive & functional assessment for patients with MCI or memory loss - MCI diagnosis disclosure & counseling on treatment options - assessment & treatment of factors contributing to MCI - avoidance of anticholinergic medications for patients with MCI - education of care partners of patients with MCI [38] * benefit of donepezil for MCI is questionable [6,56] * no difference in cognitive function scores between donepezil & placebo but lower incidence of progression to dementia (NNT = 20) [56] * benefit to risk for recommending donepezil for MCI is unfavorable [56] Clinical trials: - Ornish Intensive Lifestyle changes improved cognition in patients with mild cognitive impairment or early dementia [53]

Interactions

disease interactions

Related

Alzheimer's disease (AD) clinical dementia rating scale (CDR) neuropsychiatric features of aging

Specific

motoric cognitive risk syndrome

General

sign/symptom

References

  1. Mendez M. Comprehensive Geriatric Assessment, Osterweil et al eds, McGraw-Hill, New York, pg 86
  2. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004 - Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019 - Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  3. ADEAR Center List Manager, NIA NEWS Ronald Petersen, Ph.D., M.D., of the Mayo Clinic, Rochester, MN, Leon Thal, M.D., of the University of California, San Diego New England Journal of Medicine, April 14, 2005
  4. Fleisher AS et al, Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology 2007, 68:1588 PMID: 17287448
  5. Palmer K et al, Predictors of progression from mild cognitive impairment to Alzheimer's disease. Neurology 2007, 68:1596 PMID: 17485646
  6. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  7. Li J et al. Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease. Neurology 2011 Apr 26; 76:1485. PMID: 21490316
  8. Gomar JJ et al. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's Disease Neuroimaging Initiative. Arch Gen Psychiatry 2011 Sep; 68:961. PMID: 21893661
  9. Peterson RC. Mild cognitive impairment. N Engl J Med 2011; 364:2227-2234 PMID: 21651394
  10. Newhouse P et al. Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology 2012 Jan 10; 78:91. PMID: 22232050
  11. Plassman BL, Langa KM, Fisher GG, Heeringa SG et al Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med. 2008 Mar 18;148(6):427-34. PMID: 18347351
  12. Kinsella GJ, Mullaly E, Rand E et al Early intervention for mild cognitive impairment: a randomised controlled trial. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):730-6 PMID: 19332424
  13. Centers for Disease Control and Prevention Self-Reported Increased Confusion or Memory Loss and Associated Functional Difficulties Among Adults Aged >= 60 Years - 21 States, 2011 MMWR. May 10, 2013 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a1.htm
  14. Singh B et al. A prospective study of chronic obstructive pulmonary disease and the risk for mild cognitive impairment. JAMA Neurol 2014 Mar 17 PMID: 24637951 http://archneur.jamanetwork.com/article.aspx?articleid=1846749
  15. Albert MS, DeKosky ST, Dickson D et al The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging- Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. PMID: 21514249
  16. Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;9:CD009132. PMID: 22972133
  17. Martin M, Clare L, Altgassen AM, et al. Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst Rev. 2011;(1):CD006220. PMID: 21249675
  18. Farina N, Isaac MG, Clark AR, et al. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst Rev. 2012; 11:CD002854. PMID: 23152215
  19. Suzuki T, Shimada H, Makizako H, et al. Effects of multicomponent exercise on cognitive function in older adults with amnestic mild cognitive impairment: a randomized controlled trial. BMC Neurol. 2012;12:128. PMID: 23113898
  20. Baker LD, Frank LL, Foster-Schubert K et al Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010 Jan;67(1):71-9. PMID: 20065132
  21. Julayanont, P, Brousseay M, Chertkow H, et al. Montreal Cognitive Assessment Memory Index Score (MoCA-MIS) as a predictor of conversion from mild cognitive impairment to Alzheimer's disease. J Am Geriatr Soc. 2014;62:679-684. PMID: 24635004
  22. Vos SJB et al. Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage. Brain 2015 May; 138:1327 PMID: 25693589 http://brain.oxfordjournals.org/content/138/5/1327
  23. Marcos G, Santabarbara J, Lopez-Anton R et al. Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen's criteria. Acta Psychiatr Scand 2015 Dec 21 PMID: 26685927 http://onlinelibrary.wiley.com/doi/10.1111/acps.12543/abstract
  24. Hill NT, Mowszowski L, Naismith SL et al. Computerized cognitive training in older adults with mild cognitive impairment or dementia: A systematic review and meta-analysis. Am J Psychiatry 2016 Nov 14 PMID: 27838936
  25. Krell-Roesch J, Vemuri P, Pink A et al. Association between mentally stimulating activities in late life and the outcome of incident mild cognitive impairment, with an analysis of the APOE-epsilon4 genotype. JAMA Neurol 2017 Mar 1; 74:332. PMID: 28135351 http://jamanetwork.com/journals/jamaneurology/fullarticle/2598835
  26. Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA. 2014;312(23):2551-2561 PMID: 25514304 Free PMC Article
  27. Abner EL, Kryscio RJ, Schmitt FA et al. Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol 2017 Apr; 81:549-559 PMID: 28224671
  28. van Maurik IS, Zwan MD, Tijms BM et al Interpreting Biomarker Results in Individual Patients With Mild Cognitive Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project. JAMA Neurol. Published online October 16, 2017. PMID: 2904948 https://jamanetwork.com/journals/jamaneurology/fullarticle/2657326
  29. George J Guideline Recommends Exercise for MCI. Based on short-term evidence that twice-weekly exercise benefits cognition. MedPage Today. December 28, 2017 https://www.medpagetoday.com/neurology/generalneurology/70163 - Petersen RC, Lopez O, Armstrong MJ, et al Practice guideline update summary: Mild cognitive impairment. Neurology. 2017 Dec 27. pii: 10.1212/WNL.0000000000004826 PMID: 29282327
  30. Bartels C, Wagner M, Wolfsgruber S et al. Impact of SSRI therapy on risk of conversion from mild cognitive impairment to Alzheimer's dementia in individuals with previous depression. Am J Psychiatry 2017 Nov 28 PMID: 29179578 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2017.17040404
  31. Petersen RC, Lopez O, Armstrong MJ et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2018 Jan 16; 90:126-135. PMID: 29282327 http://n.neurology.org/content/90/3/126
  32. Belleville S, Hudon C, Bier N et al. MEMO+: Efficacy, durability and effect of cognitive training and psychosocial intervention in individuals with mild cognitive impairment. J Am Geriatr Soc 2018 Apr; 66:655. PMID: 29313875
  33. Albert M, Zhu Y, Moghekar A et al. Predicting progression from normal cognition to mild cognitive impairment for individuals at 5 years. Brain 2018 Mar; 141:877 PMID: 29365053 https://academic.oup.com/brain/article/141/3/877/4818093
  34. Hu J, Jia J, Zhang Y, Miao R, Huo X, Ma F. Effects of vitamin D3 supplementation on cognition and blood lipids: A 12-month randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2018 Oct 2; PMID: 30279212 https://jnnp.bmj.com/content/early/2018/10/01/jnnp-2018-318594 - Fujishiro H. Vitamin D3 as a potentially modifiable factor in mild cognitive impairment. J Neurol Neurosurg Psychiatry 2018 Oct 2 PMID: 30279214 https://jnnp.bmj.com/content/early/2018/10/01/jnnp-2018-319021
  35. Blumenthal JA, Smith PJ, Mabe S et al Lifestyle and neurocognition in older adults with cognitive impairments. A randomized trial. Neurology. Dec 19, 2018 PMID: 30568005 http://n.neurology.org/content/early/2018/12/19/WNL.0000000000006784
  36. The SPRINT MIND Investigators for the SPRINT Research Group Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia. A Randomized Clinical Trial. JAMA. Published online January 28, 2019 PMID: 30686041 https://jamanetwork.com/journals/jama/fullarticle/2723256 - Yaffe K Prevention of Cognitive Impairment With Intensive Systolic Blood Pressure Control. JAMA. Published online January 28, 2019 PMID: 30688980 https://jamanetwork.com/journals/jama/fullarticle/2723255
  37. Boyle PA, Yu L, Schneider JA, Wilson RS, Bennett DA. Scam awareness related to incident Alzheimer dementia and mild cognitive impairment: A prospective cohort study. Ann Intern Med 2019 Apr 16; PMID: 30986826 https://annals.org/aim/article-abstract/2731121/scam-awareness-related-incident-alzheimer-dementia-mild-cognitive-impairment-prospective
  38. Foster NL, Bondi MW, Das R et al Quality improvement in neurology. Mild cognitive impairment quality measurement set. Neurology 2019 Sep 18; PMID: 31534026 https://n.neurology.org/content/93/16/705
  39. van Maurik IS et al. Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): A modelling study. Lancet Neurol 2019 Nov; 18:1034 PMID: 31526625 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(19)30283-2/fulltext
  40. Ma F, Wu T, Miao R, Xiao YY, Zhang W, Huang G. Conversion of mild cognitive impairment to dementia among subjects with diabetes: a population-based study of incidence and risk factors with five years of follow-up. J Alzheimers Dis. 2015;43(4):1441-9. PMID: 25159674
  41. Hughes D et al. Association of blood pressure lowering with incident dementia or cognitive impairment: A systematic review and meta-analysis. JAMA 2020 May 19; 323:1934. PMID: 32427305 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2766163
  42. Ebenau JL et al. ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project. Neurology 2020 Jul 7; 95:e46.
  43. Meglio M Health-Deficit Accumulation Affects Risk for Mild Cognitive Impairment, Dementia. NeurologyLive. 2020. Nov 17. https://www.neurologylive.com/view/health-deficit-accumulation-affects-chance-of-mild-cognitive-impairment-dementia
  44. Weigand AJ et al. Association of anticholinergic medications and AD biomarkers with incidence of MCI among cognitively normal older adults. Neurology 2020 Oct 20; 95:e2295 PMID: 32878992 https://n.neurology.org/content/95/16/e2295
  45. Andrews M Trouble Managing Money May Be an Early Sign of Dementia. Annals of Long-Term Care. May 5, 2021 https://www.managedhealthcareconnect.com/annals-long-term-care/trouble-managing-money-may-be-early-sign-dementia
  46. Angevaare MJ, Vonk JMJ, Bertoola L et al. Predictors of incident mild cognitive impairment and its course in a diverse community-based population. Neurology 2022 Jan 4; 98:e15. PMID: 34853178 PMCID: PMC8726570 Free PMC article https://n.neurology.org/content/98/1/e15
  47. Butler M, McCreedy E, Nelson VA et al. Does cognitive training prevent cognitive decline? a systematic review. Ann Intern Med. 2018;168(1):63-68 PMID: 29255842 Free article https://www.acpjournals.org/doi/10.7326/M17-1531 - Butler M, Nelson VA, Davila H et al. Over-the-counter supplement interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia: a systematic review. Ann Intern Med. 2018;168(1):52-62 PMID: 29255909 Free article
  48. George J Some Interventions Improve Cognition in Older Adults More Than Others. Multidomain programs led to better outcomes in people with mild cognitive impairment. MedPage Today May 3, 2022 https://www.medpagetoday.com/neurology/dementia/98526 - Salzman T, Sarquis-Adamson V, Son S et al Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment. A Systematic Review and Meta-analysis. JAMA Netw Open. 2022;5(5):e226744 PMID: 35503222 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791809
  49. George J Cognition Boosted by Thinking Positively About Aging. Adults with mild cognitive impairment more likely to recover if they held positive age beliefs. MedPage Today April 12, 2023 https://www.medpagetoday.com/neurology/generalneurology/103974 - Levy BR, Slade MD Role of Positive Age Beliefs in Recovery From Mild Cognitive Impairment Among Older Persons. JAMA Netw Open. 2023;6(4):e237707. PMID: 37043204 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2803740
  50. NEJM Knowledge+ Psychiatry
  51. Tangalos EG, Petersen RC. Mild Cognitive Impairment in Geriatrics. Clin Geriatr Med. 2018 Nov;34(4):563-589. PMID: 30336988 Review.
  52. Montero-Odasso M, Zou G, Speechley M et al Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2324465. PMID: 37471089 PMCID: PMC10359965 Free PMC article. Clinical Trial.
  53. George J Alzheimer's Slowed by Intensive Lifestyle Changes Small trial led by Dean Ornish, MD, shows cognitive improvement. MedPage Today June 11, 2024 https://www.medpagetoday.com/neurology/alzheimersdisease/110596 - Ornish D, Madison C, Kivipelto M et al. Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer's disease: a randomized, controlled clinical trial. Alzheimers Res Ther. 2024. Jun 7;16(1):122. PMID: 38849944 PMCID: PMC11157928 Free PMC article. Clinical Trial.
  54. George J Well-Being Declines Before Mild Cognitive Impairment. Two components hit hardest: purpose in life and personal growth. MedPage Today, August 13, 2024 https://www.medpagetoday.com/neurology/dementia/111501 - Guo J, Wang J, Dove A, Bennett DA, Xu W. Psychological well-being trajectories preceding incident mild cognitive impairment and dementia. J Neurol Neurosurg Psychiatry. 2024 Aug 13:jnnp-2024-333837. PMID: 39137975
  55. Liu L, Zhang CS, Zhang AL, et al. Oral Chinese herbal medicine combined with donepezil for mild cognitive impairment: A systematic review and meta-analysis. J Am Geriatr Soc. 2024 Aug 12 PMID: 39134455 https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.19125
  56. Matsunaga S, Fujishiro H, Takechi H. Efficacy and Safety of Cholinesterase Inhibitors for Mild Cognitive Impairment: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2019 Aug 12;71(2):513-523. PMID: 31424411