Mild cognitive impairment

Mild cognitive impairment (MCI) is a neurological disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of daily living.[1] MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimer's disease.[2] It includes both memory and non-memory impairments.[3]

Mild Cognitive Impairment
Other namesIncipient dementia, isolated memory impairment
SpecialtyNeurology
SymptomsCan include memory impairments (amnestic) or cognitive problems like impaired decision making, language, or visuospatial skills (non-amnestic)
Usual onsetTypically appears in adults 65 or older
TypesAmnestic, non-amnestic
Risk factorsAge, family history, cardiovascular disease
Diagnostic methodBased on symptoms assessed by a clinical neuropsychologist through observations, neuroimaging, and blood tests

The cause of the disorder remains unclear, as well as its prevention and treatment.

Classification

MCI can present with a variety of symptoms, but is divided generally into two types.[4]

Amnestic MCI (aMCI) is mild cognitive impairment with memory loss as the predominant symptom; aMCI is frequently seen as a prodromal stage of Alzheimer's disease.[4][3][5] Studies suggest that these individuals tend to progress to probable Alzheimer's disease at a rate of approximately 10% to 15% per year.[6]

Nonamnestic MCI (naMCI) is mild cognitive impairment in which impairments in domains other than memory (for example, language, visuospatial, executive) are more prominent.[4][7] It may be further divided as nonamnestic single- or multiple-domain MCI and these individuals are believed to be more likely to convert to other dementias (for example, dementia with Lewy bodies).[8]

Causes

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.

Risk factors of both dementia and MCI are considered to be the same. They are ageing, genetic (heredity) cause of Alzheimer’s or other dementia, and risk of cardiovascular disease.[9]

Individuals with MCI have increased oxidative damage in their nuclear and mitochondrial brain DNA.[10] A widely studied biomarker of DNA damage, 8-hydroxyguanine was found to be elevated in nuclear DNA of the frontal and temporal lobe of individuals with MCI and in mitochondrial DNA of the temporal lobe compared with age matched control subjects.[10] Other oxidized DNA bases were also increased in the brains of individuals with MCI. These findings suggested that oxidative damage to DNA occurs in the earliest detectable phase of Alzheimer’s disease and thus may play a significant role in the pathogenesis of this disease.[10]

Diagnosis

The diagnosis of MCI requires considerable clinical judgement,[6] and as such a comprehensive clinical assessment including clinical observation, neuroimaging,[11] blood tests and neuropsychological testing are best in order to rule out an alternate diagnosis. MCI is diagnosed when there is:[12]

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

Neuropathology

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.[13] Alternatively, many individuals develop neurofibrillary tangles without amyloid, a pattern termed primary age-related tauopathy.

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.[14] 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.[15] Another tool aimed at predicting the progression of MCI to Alzheimer's disease dementia, known as 18F PET with florbetaben shows promise but further study is needed to demonstrate diagnostic test accuracy with larger trials.[16] Such tools may help greatly in assisting clinical research for therapies.

Treatment
See also: Neurobiological effects of physical exercise

As of January 2018, there are no USFDA-approved medications for the treatment of mild cognitive impairment.[4] Moreover, as of January 2018, there is no high-quality evidence that supports the efficacy of any pharmaceutical drugs or dietary supplements for improving cognitive symptoms in individuals with mild cognitive impairment.[4] A moderate amount of high-quality evidence supports the efficacy of regular physical exercise for improving cognitive symptoms in individuals with MCI.[4] The clinical trials that established the efficacy of exercise therapy for MCI involved twice weekly exercise over a period of six months.[4] A small amount of high-quality evidence supports the efficacy of cognitive training for improving some measures of cognitive function in individuals with mild cognitive impairment.[4] Due to the heterogeneity among studies which assessed the effect of cognitive training in individuals with MCI, there are no particular cognitive training interventions that have been found to provide greater symptomatic benefits for MCI relative to other forms of cognitive training.[4]

The American Academy of Neurology's (AAN) clinical practice guideline on mild cognitive impairment from January 2018 stated that clinicians should identify modifiable risk factors in individuals with MCI, assess functional impairments, provide treatment for any behavioral or neuropsychiatric symptoms, and monitor the individual's cognitive status over time.[4] It also stated that medications which cause cognitive impairment should be discontinued or avoided if possible.[4] Due to the lack of evidence supporting the efficacy of cholinesterase inhibitors in individuals with MCI, the AAN guideline stated that clinicians who choose to prescribe them for the treatment of MCI must inform patients about the lack of evidence supporting this therapy.[4] The guideline also indicated that clinicians should recommend that individuals with MCI engage in regular physical exercise for cognitive symptomatic benefits;[4] clinicians may also recommend cognitive training, which appears to provide some symptomatic benefit in certain cognitive measures.[4]

As MCI may represent a prodromal state to clinical Alzheimer's disease, treatments proposed for Alzheimer's disease, such as antioxidants and cholinesterase inhibitors, could potentially be useful; however, As of January 2018, there is no evidence to support the efficacy of cholinesterase inhibitors for the treatment of mild cognitive impairment.[4]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;[17] donepezil showed only minor, short-term benefits and was associated with significant side effects.[18]

Outlook

MCI does not usually interfere with daily life, but around 50 percent of people diagnosed with it go on to develop the far more severe Alzheimer's disease within five years (mainly for people diagnosed with the amnestic type). This diagnosis can also serve as an earlier indicator for other types of dementia. However, some instances of MCI may simply remain stable over time or even remit.[4] Individuals diagnosed with MCI should seek reevaluation of symptoms every six months to ensure that the condition has not progressed. [19] In any case, it is recommended that people start seeking help as soon as any cognitive changes appear since this can lead to a diagnosis or possible treatments.[20]

Prevalence

The prevalence of MCI varies by age.[4] The prevalence of MCI among different age groups is as follows: 6.7% for ages 60–64; 8.4% for ages 65–69, 10.1% for ages 70–74, 14.8% for ages 75–79, and 25.2% for ages 80–84.[4] After a two-year follow-up, the cumulative incidence of dementia among individuals who are over 65 years old and were diagnosed with MCI was found to be 14.9%.[4]

Globally, approximately 16% of the population over the age of 70 experiences some type of mild cognitive impairment.

See also
  • Menopause-related cognitive impairment – similar symptoms, but appears shortly after menopause, and can be treated with hormone replacement therapy

References
  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. Petersen RC, Bennett D (June 2005). "Mild cognitive impairment: is it Alzheimer's disease or not?". J. Alzheimers Dis. 7 (3): 241–5. doi:10.3233/jad-2005-7307. PMID 16006668.
  3. Yu J, Lam CL, Lee TM (December 2017). "White matter microstructural abnormalities in amnestic mild cognitive impairment: A meta-analysis of whole-brain and ROI-based studies". Neurosci Biobehav Rev (Meta-analysis and review). 83: 405–416. doi:10.1016/j.neubiorev.2017.10.026. PMID 29092777.
  4. Petersen RC, Lopez O, Armstrong MJ, et al. (January 2018). "Practice guideline update summary: Mild cognitive impairment – Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology". Neurology. Special article. 90 (3): 126–135. doi:10.1212/WNL.0000000000004826. PMC 5772157. PMID 29282327. Lay summary – Exercise may improve thinking ability and memory (27 December 2017). In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures. ... Clinicians should recommend regular exercise (Level B). ... Recommendation: For patients diagnosed with MCI, clinicians should recommend regular exercise (twice/week) as part of an overall approach to management (Level B).
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  8. 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.
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  16. Martínez G, Vernooij RW, Fuentes Padilla P, et al. (November 2017). "18F PET with florbetaben for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI)". Cochrane Database Syst Rev. 11: CD012883. doi:10.1002/14651858.CD012883. PMC 6485979. PMID 29164600.
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Classification
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