Mild Cognitive Impairment – A precursor to Alzheimer’s disease or other dementias?

It has been recognized for many years that people may have minor memory problems before a diagnosis of dementia can be made. The ageing population and the widespread continuing community discussion on Alzheimer’s disease (AD) have resulted in increased awareness by the community of dementia and memory disorders. The most recently introduced term to describe minor memory disorders, mild cognitive impairment, or MCI, by researchers at the Mayo Clinic USA has been useful to allow medical researchers to focus on the whether people with minor memory problems develop greater problems over time or whether their problem remains static. Some researchers believe that many if not all persons with MCI may develop dementia. This field of research has evolved significantly in the last 5 years and is likely to continue to change until sufficient numbers of subjects with MCI are followed for many years.

There has been considerable variability in the reported rates of progression of MCI to AD. The rate of progression of an illness has implications for prevention as well as treatment of those with disease. It appears lower in studies that recruit subjects from the community (1) compared to clinic based studies (2). Some studies have reported improvements in scores in some subjects, but usually the study has found that MCI subjects are at risk of progression of their memory problems so that some eventually develop AD. More recent studies have tried to distinguish a group of subjects with memory impairment only, or “amnestic” form MCI from other forms of MCI in which judgement or initiative are sometimes affected. Two criteria are usually applied for the diagnosis of amnestic MCI, firstly a complaint or recognition of a memory problem by the subject and secondly a performance on a standardized memory test with a score about 1.5 standard deviations or more below normal in the absence of other problems, such as depression, excessive alcohol use, vitamin B12 or thyroid disorder (2). Although it seems obvious that reduced performance on memory-related tasks predict progression to AD, reductions in performance in other cognitive domains together with reductions in memory-related tasks is a more likely to predict progression to AD (3) than memory problems alone. Furthermore, imaging studies both MRI and PET, of this group who develop AD find more extensive changes in the brain than just those areas concerned with memory (4, 5). Such studies look at group differences; it is significantly harder to discern MRI differences between normal subjects and individuals with MCI, unlike AD where temporal atrophy or ventricular enlargement is usual.Usually people with cognitive complaints that do not have dementia request advice about how to prevent or delay further problems. Physical exercise may promote brain health, through prevention or slowing of cognitive decline in well persons with a halving of risk through regular exercise in mid life even when allowing for other vascular risk factors (6). Mental activities, such as reading, studying, doing puzzles, social activities, volunteer activities and gardening were all associated with a significant reduction in dementia risk in subjects aged over 75 years when re-evaluated 6 years later (7). Thus significant recent work suggests that the old adage about “use it or lose it” has some rational basis. Similarly, well recognized vascular risk factors have also been associated with increased risk of dementia, with obesity (Body mass index greater than 30)*, hypertension and hypercholesterolemia all each doubling the risk of dementia independently and these factors add to increase the risk further (8). Such studies have not examined whether these risk factors are implicated for MCI. Other patients with memory complaints have read about PET-based compounds that can detect amyloid load. The use of such compounds, although likely to provide researchers with new insights about disease such as AD and their possible precursor states such as MCI, are restricted to research studies at present(9, 10). Thus in the past few years there has been some reworking of ideas about altered thinking prior to the onset of frank cognitive impairment. A group of at-risk subjects, those with amnestic MCI, are at increased risk of developing AD. Although there has been significant interest in genetic factors contributing to AD, it appears at present as if environmental or lifestyle factors, such as exercise and mental activities may delay the onset of the illness. Such observations have profound public health implications when the cost of such activities are considered against the costs of providing care for persons in nursing homes. * Body mass index – calculated by dividing the mass of a person (kg) by their height in metres squared. For example 100kg/2 * 2metres = 25 . The normal range is 20 to 25. Dr Jonathon Chalk, MBBS, FRACP, PhDUniversity of QueenslandVirtual Neuro Centre, EAB Member1. Daly E, Zaitchik D, Copeland M, Schmahmann J, Gunther J, Albert M. Predicting conversion to Alzheimer disease using standardized clinical information. Arch Neurol 2000;57(5):675-80.2. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 1999;56(3):303-8.3. Palmer K, Backman L, Winblad B, Fratiglioni L. Detection of Alzheimer’s disease and dementia in the preclinical phase: population based cohort study. Bmj 2003;326(7383):245.4. Fox NC, Crum WR, Scahill RI, Stevens JM, Janssen JC, Rossor MN. Imaging of onset and progression of Alzheimer’s disease with voxel-compression mapping of serial magnetic resonance images. Lancet 2001;358(9277):201-5.5. Silverman DH, Small GW, Chang CY, et al. Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. Jama 2001;286(17):2120-7.6. Rovio S, Kareholt I, Helkala EL, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 2005;4(11):705-11.7. Wang HX, Karp A, Winblad B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen project. Am J Epidemiol 2002;155(12):1081-7.8. Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol 2005;62(10):1556-60.9. Klunk WE, Engler H, Nordberg A, et al. Imaging the pathology of Alzheimer’s disease: amyloid-imaging with positron emission tomography. Neuroimaging Clin N Am 2003;13(4):781-9, ix.10. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004;55(3):306-19.