What is Mild Cognitive Impairment (MCI) and why does it matter?

Defining MCI

Most people with dementia go through a prodromal stage in which they or those close to them note that their memories are poor, but they are still able to cope with their normal routines and do not fulfil the diagnostic criterion for dementia of experiencing significant impairment of social or occupational functioning. The term Mild Cognitive Impairment (MCI) emerged in the 1990s in succession to a previous series of diagnostic entities dating back to 1962 which has included such terms as Benign Senescent Forgetfulness and Age Associated Memory Impairment. Current concepts of MCI grew out of work in Rochester, USA1 where individuals presenting with memory complaints were assessed in detail and followed over long periods of time. In the series followed in Rochester and later in cohorts observed elsewhere, those individuals who presented with concerns that their memories were impaired, who scored 1.5 standard deviations or more below the age and education adjusted mean on at least one neuropsychological memory test, and who did not have ‘significant’ impairment of social or occupational functioning, it was found that around two thirds of these individuals eventually developed dementia (usually due to Alzheimer’s disease (AD)) while one third did not develop dementia during follow-up. The rate at which dementia developed was between 10-20% per annum2.

The purposes of defining a condition that has a high risk of conversion to dementia include delineating a population in which putative therapeutic interventions that may slow or prevent decline can be studied.

The carriage of an APOE ε4 allele (carried by 25% of European derived populations, and known to triple the risk of dementia due to AD at any age), and the presence of high levels of Aβ42 amyloid protein on amyloid imaging (an experimental nuclear medicine technique using a variety of radioactive ligands) or a high ration of tau to amyloid protein in the CSF all are associated with a high likelihood of progression of cognitive decline in MCI. Recently developed research criteria for “Prodromal Alzheimer’s Disease” require the manifestation of an MCI syndrome in the presence of a positive biomarker result (amyloid imaging or CSF tau/amyloid ratio) and have the potential to define a population that might be helped by strategies to diminish amyloid production or to increase its clearance from the brain, as current thinking posits that amyloid production leads over decades to irreversible neuronal damage3.

Does anything help?

Prospective trials of cholinesterase inhibitors (donepezil, rivastigmine and galantamine) show that while they are helpful for mild and moderate dementia due to AD, they are of no benefit in delaying the transition of MCI to frank dementia, and the same applies to Vitamin E and gingko4.

At least one study of regular physical exercise (typically 150 minutes of brief walking per week)5 suggests that such activity may be of modest benefit in slowing cognitive decline in MCI. Other evidence implies that social engagement and continued intellectual activity may also have some beneficial effect on maintenance of cognitive function, but those these effects do not appear to be very large6 7.

What to do with diagnosed MCI patients?

Patients diagnosed with MCI deserve honest diagnostic disclosure about their prognosis and the possible benefits of exercise and other activities. It is usual to follow such patients every six months or so in order that dementia can be diagnosed promptly if it does appear, as there is evidence that cholinesterase inhibitors are helpful treatments once the stage of mild dementia due to AD has been reached.

Some individuals with MCI are keen to enter research studies of putative therapies that may slow progression of cognitive decline and delay the onset of dementia. Such studies include trials of dietary intervention, regular exercise, cognitive stimulation, or combinations of these. Other research now ongoing in Melbourne and many other sites around the world offers individuals who fulfil research criteria for prodromal AD the chance to participate in double blind placebo controlled trials of drugs which may diminish amyloid production or aid in its removal from the brain via monoclonal antibodies which bind to Aβ42 amyloid or its derivatives. Sites undertaking such work including the Howard Florey Research Institute’s Mental Health Research Institute (MHRI) Campus in Parkville and the Clinical Trials Centre at the Austin Hospital’s West Heidelberg campus. These studies offer the prospect that within five years or so we will know if slowing cognitive decline in late life will turn out to be a realistic prospect for large numbers of older people.

Conflict of interest declaration

David Ames is a site investigator for Eli Lilly’s Amaranth β secretase inhibitor trial at the Parkville MHRI site.

Important topics to consider in the management of MCI

  • Disclosure of diagnosis
  • Information on assessment results
  • Indvidualised information on prognosis
  • Pharmacological management options
  • Non-phamarmacological approaches
  • Information on research trials in the area
  • Monitoring health and vascular risk factors
  • Neuropsychiatric symptoms
  • Discuss ADLs (including driving)
  • Planning the future (e.g. finances, travelling, etc.)
  • Information on AD treatment in case of progression
  • “Carer” burden
  • Information on useful contacts (e.g. Alzheimer Association)
  • Regular follow-up appointments

References:
1. PETERSEN, R.C. (2007) Mild cognitive impairment: current research and clinical implications. Seminars in Neurology, 27, 1, 22-31.
2. ALBERT M. S., DEKOSKY, S. T., DICKSON, D., et al. (2011) 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, 7, 270-9.
3. VILLEMAGNE VL, BURNHAM S, BOURGEAT P, et al. (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol., 12: 357-367.
4. RUSS, T.C., MORLING, J.R. (2012) Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst. Rev., 9, CD009132.
5. LAUTENSCHLAGER, N.T., COX, K.L., FLICKER, L. et al. (2008) Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA, 300 (9), 1027-1037.
6. KARP, A., PAILLARD-BORG, S., WANG, H.X., SILVERSTEIN, M., WINBLAD, B. & FRATIGLIONI, L. (2006) Mental, physical and social components in leisure activities equally contribute to decrease dementia risk. Dement Geriatr Cogn Disord., 21(2), 65-73.
7. MARTIN, M., CLARE, L., ALTGASSEN, A.M., et al., (2011) Cognition-based interventions for healthy older people and people with mild cognitive impairment. Cochrane Database Syst Rev.,19(1), 1-51.

 


Prof David AmesAUTHOR | Prof David Ames 
Prof Ames specialises in old age psychiatry and particularly the assessment and management of late life cognitive decline and dementia, He has extensive experience in the early diagnosis and management of cognitive difficulties and has published extensively in this field.

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PH | 03 9805 4309  EMAIL dames@unimelb.edu.au

 

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