Mild cognitive impairment

Mild cognitive impairment
Classification and external resources
Specialty psychiatry
ICD-10 F06.7
ICD-9-CM 331.83
Patient UK Mild cognitive impairment
MeSH D060825

Mild cognitive impairment (MCI, also known as incipient dementia, or isolated memory impairment) is a brain function syndrome involving the onset and evolution of cognitive impairments beyond those expected based on the age and education of the individual, but which are not significant enough to interfere with their daily activities.[1] It may occur as a transitional stage between normal aging and dementia. Although MCI can present with a variety of symptoms, when memory loss is the predominant symptom it is termed "amnestic MCI" and is frequently seen as a prodromal stage of Alzheimer's disease.[2] Studies suggest that these individuals tend to progress to probable Alzheimer’s disease at a rate of approximately 10% to 15% per year.[2]

Additionally, when individuals have impairments in domains other than memory it is classified as nonamnestic single- or multiple-domain MCI and these individuals are believed to be more likely to convert to other dementias (e.g., dementia with Lewy bodies).[3] However, some instances of MCI may simply remain stable over time or even remit. Causation of the syndrome in and of itself remains unknown, as therefore do prevention and treatment.


According to some experts, mild cognitive impairment (MCI) may be caused due to alteration in the brain triggered during early stages of Alzheimer’s disease or other forms of dementia. However, exact causes of MCI are still unknown.

But, risk factors of both dementia and MCI are considered to be the same. They are aging, genetic (heredity) cause of suffering from Alzheimer’s or other dementia, and risk of cardiovascular disease. [4]


The diagnosis of MCI requires considerable clinical judgement,[2] and as such a comprehensive clinical assessment including clinical observation, neuroimaging, blood tests and neuropsychological testing are best in order to rule out an alternate diagnosis. MCI is diagnosed when there is:[5]

  1. Evidence of memory impairment
  2. Preservation of general cognitive and functional abilities
  3. Absence of diagnosed dementia


There is evidence suggesting that although amnestic MCI patients may not meet neuropathologic criteria for Alzheimer's disease, patients may be in a transitional stage of evolving Alzheimer's disease; patients in this hypothesized transitional stage demonstrated diffuse amyloid in the neocortex and frequent neurofibrillary tangles in the medial temporal lobe.[6]

There is emerging evidence that magnetic resonance imaging can observe deterioration, including progressive loss of gray matter in the brain, from mild cognitive impairment to full-blown Alzheimer disease.[7] A technique known as PiB PET imaging is used to clearly show the sites and shapes of beta amyloid deposits in living subjects using a C11 tracer that binds selectively to such deposits.[8] Such tools may help greatly in assisting clinical research for therapies.


There is no proven treatment or therapy for mild cognitive impairment. As MCI may represent a prodromal state to clinical Alzheimer’s disease, treatments proposed for Alzheimer’s disease, such as antioxidants and cholinesterase inhibitors, may be useful. Two drugs used to treat Alzheimer's disease have been assessed for their ability to treat MCI or prevent progression to full Alzheimer's disease. Rivastigmine failed to stop or slow progression to Alzheimer's disease or to improve cognitive function for individuals with mild cognitive impairment,[9] and donepezil showed only minor, short-term benefits and was associated with significant side effects.[10]

A new form of magnesium, namely magnesium l–threonate, has surfaced as a promising avenue in the treatment of cognitive impairment. This form is capable of delivering high amounts of magnesium to the central nervous system and has in preclinical animal studies shown remarkable results, even reversing advanced Alzheimers in some cases.[11] These findings have now been replicated in the first double-blind placebo controlled human trial which showed similar efficacy in treating cognitive impairment as the animal studies.[12] If corroborated by further human studies this could very well be a landmark in the treatment of age-related cognitive impairment (for which there is presently no effective treatment). The results of this study are also in line with systematic reviews showing that Alzheimer’s patients have lower magnesium status when compared to healthy controls.[13] Despite its apparent simplicity, just replenishing the brains stores of a vital mineral, this study parallels recent findings in other domains of neurobiology, for example the finding that a new copper formulation is able to halt the progression of amyotrophic lateral sclerosis.[14]

In a two-year randomized trial of 168 people with MCI given either high-dose vitamins or placebo, vitamins cut the rate of brain shrinkage by up to half. The vitamins were the three B vitamins folic acid, vitamin B6, and vitamin B12, which inhibit production of the amino acid homocysteine. High blood levels of homocysteine are associated with increased risk of cognitive decline,[15] dementia, and cardiovascular disease.[16][17][18]

Non-pharmacological experimental treatments include transcranial magnetic stimulation and transcranial direct current stimulation.[19]

New observation

Recent studies have shown A possible connection between macronutrient intake and development of MCI

It is suggested that A dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk of MCI or dementia in elderly persons [20]


  1. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999). "Mild cognitive impairment: clinical characterization and outcome". Arch. Neurol. 56 (3): 303–8. doi:10.1001/archneur.56.3.303. PMID 10190820.
  2. 1 2 3 Grundman M, Petersen RC, Ferris SH, et al. (2004). "Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials". Arch. Neurol. 61 (1): 59–66. doi:10.1001/archneur.61.1.59. PMID 14732621.
  3. Tabert MH, Manly JJ, Liu X, et al. (2006). "Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment". Arch. Gen. Psychiatry. 63 (8): 916–24. doi:10.1001/archpsyc.63.8.916. PMID 16894068.
  4. Mild Cognitive Impairment, Retrieved 3rd February 2016.
  5. Morris, J C.; Storandt, M.; Miller, J. P.; McKeel, D. W.; Price, J. L.; Rubin, E.H. & Berg, L. (2001). "Mild cognitive impairment represents early-stage Alzheimer disease". Archives of Neurology. 58 (3): 387–405. doi:10.1001/archneur.58.3.397.
  6. Petersen RC, Parisi JE, Dickson DW, et al. (2006). "Neuropathologic features of amnestic mild cognitive impairment". Arch. Neurol. 63 (5): 665–72. doi:10.1001/archneur.63.5.665. PMID 16682536.
  7. Whitwell JL, Shiung MM, Przybelski SA, et al. (2008). "MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment". Neurology. 70 (7): 512–20. doi:10.1212/01.wnl.0000280575.77437.a2. PMC 2734138Freely accessible. PMID 17898323.
  8. Jack CR, Lowe VJ, Senjem ML, et al. (2008). "11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment" (pdf). Brain. 131 (Pt 3): 665–80. doi:10.1093/brain/awm336. PMC 2730157Freely accessible. PMID 18263627.
  9. Feldman HH, Ferris S, Winblad B, et al. (2007). "Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study". Lancet Neurol. 6 (6): 501–12. doi:10.1016/S1474-4422(07)70109-6. PMID 17509485.
  10. Birks J, Flicker L (2006). Birks J, ed. "Donepezil for mild cognitive impairment". Cochrane Database Syst Rev. 3: CD006104. doi:10.1002/14651858.CD006104. PMID 16856114.
  11. Li W, Yu J, Liu Y, Huang X, Abumaria N, Zhu Y, Huang X, Xiong W, Ren C, Liu XG, Chui D, Liu G (2014). "Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model". Molecular Brain. 7 (65): 1–20. doi:10.1186/s13041-014-0065-y. PMC 4172865Freely accessible. PMID 25213836.
  12. Liu G, Weinger JG, Lu ZL, Xue F, Sadeghpour S (2015). "Efficacy and safety of MMFS-01, a synapse density enhancer, for treating cognitive impairment in older adults: a randomized, double-blind, placebo-controlled trial". Journal of Alzheimer's disease. 49 (4): 971–990. doi:10.3233/JAD-150538. PMC 4927823Freely accessible. PMID 26519439.
  13. Veronese N, Zurlo A, Solmi M, Luchini C, Trevisan C, Bano G, Manzato E, Sergi G, Rylander R (2016). "Magnesium Status in Alzheimer's Disease: A Systematic Review". American journal of Alzheimer's disease and other dementias. 31 (3): 208–213. doi:10.1177/1533317515602674. PMID 26351088.
  14. Williams JR, Trias E, Beilby PR, Lopez NI, Labut EM, Bradford CS, Roberts BR, McAllum EJ, Crouch PJ, Rhoads TW, Pereira C, Son M, Elliott JL, Franco MC, Estévez AG, Barbeito L, Beckman JS (2016). "Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.". Neurobiology of disease. 89 (4): 1–9. doi:10.1016/j.nbd.2016.01.020. PMID 26826269.
  15. McCaddon,A.; et al. (2001). "Homocysteine and cognitive decline in healthy elderly". Dement Geriatr Cogn Disord. 12 (5): 309–313. doi:10.1159/000051275. PMID 11455131.
  16. Kelland, K. (2010). B vitamins found to halve aging brain shrinkage. Reuters Health.
  17. Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H (2010). "Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial". PLoS ONE. 5 (9): e12244. doi:10.1371/journal.pone.0012244. PMC 2935890Freely accessible. PMID 20838622.
  18. Ravaglia, G.; Forti, P.; Maioli, F.; Matelli, M.; Servadei, L.; Nicoletta, B.; Porcellini E. & Licastor, F. (2005). "Homocysteine and folate as risk factors for dementia and Alzheimer disease". the American Journal of Clinical Nutrition. 82 (3): 636–643. PMID 16155278.
  19. Alencastro, A.S.; Pereira, D.A.; Brasil-Neto, J.P. (2015). "Transcranial direct current stimulation in mild cognitive impairment: methodology for a randomized controlled trial.". PeerJ PrePrints. 3:e1610v1. doi:10.7287/peerj.preprints.1610v1.
  20. Relative Intake of Macronutrients Impacts Risk of Mild Cognitive Impairment or Dementia


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