Mild cognitive impairment
Mild cognitive impairment (MCI) is a neurocognitive 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. MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimer's disease. It includes both memory and non-memory impairments. The cause of the disorder remains unclear, as well as its prevention and treatment. Mild cognitive impairment has been relisted as mild neurocognitive disorder in DSM-5, and in ICD-11, the latter effective on the 1st of  January 2022. Classification. MCI can present with a variety of symptoms, but is divided generally into two types. 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. Studies suggest that these individuals tend to progress to probable Alzheimer's disease at a rate of approximately 10% to 15% per year. It is possible that being diagnosed with cognitive decline may serve as an indicator of MCI. Nonamnestic MCI (naMCI) is mild cognitive impairment in which impairments in domains other than memory (for example , language, visuospatial, executive) are more prominent. 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). The International Classification of Diseases classifies MCI as a "mental and behavioural disorder." 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 aging, genetic (heredity) cause of Alzheimer's or other dementia, and risk of cardiovascular disease. Individuals with MCI have increased oxidative damage in their nuclear and mitochondrial brain DNA. 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. 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. Diagnosis. The diagnosis of MCI requires considerable clinical judgement, 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: 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. 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. 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 C tracer that binds selectively to such deposits. 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. Such tools may help greatly in assisting clinical research for therapies. Treatment. there are no USFDA-approved medications for the treatment of mild cognitive impairment. 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. A moderate amount of high-quality evidence supports the efficacy of regular physical exercise for improving cognitive symptoms  in individuals with MCI. The clinical trials that established the efficacy of exercise therapy for MCI involved twice weekly exercise over a period of six months. 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. 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. 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. It also stated that medications which cause cognitive impairment "should" be discontinued or avoided if possible. 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. The guideline also indicated that clinicians "should" recommend that individuals with MCI engage in regular physical exercise for cognitive symptomatic benefits; clinicians "may" also recommend cognitive training, which appears to provide some symptomatic benefit in certain cognitive measures. 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. 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; donepezil showed only minor, short-term benefits and was associated with significant side effects. Interventions. For people with mild cognitive impairment. Current evidence suggests that cognition-based interventions do improve mental performance (i.e. memory, executive function, attention, and speed) in older adults and people with mild cognitive impairment. Especially, immediate and delayed verbal recall resulted in higher performance gains from memory training . Carbohydrates for improving the cognitive performance. There is currently limited evidence to form a strong conclusion to recommend the use of any form of carbohydrate in preventing or reducing cognitive decline in older adults with normal cognition or mild cognitive impairment. So, more large and higher quality evidence is needed to evaluate memory improvement and find nutritional issues due to carbohydrates. 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. Individuals diagnosed with MCI should seek reevaluation of symptoms every six months to ensure that the condition has not progressed. 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. Prevalence. The prevalence of MCI varies by age. 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. 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%. Globally, approximately 16% of the population over the age of 70 experiences some type of mild cognitive impairment.