Does Does Mild Cognitive Impairment (MCI) inevitably progress to dementia?

/Home/Caregiving and Alzheimer's/Caregiving for Mild Cognitive Impairment (MCI)

Your loved one has been diagnosed with "Mild Cognitive Impairment (MCI)". Does that mean that your loved one will inevitably develop Alzheimer's?

No.

Some patients do go on to develop dementia, but others hold steady at their mild level of impairment, and some actually revert to normal. For example, one study showed that over almost 3 years, 20% of MCI sufferers had recovered and an additional 60% neither improved nor deteriorated. (Wolf H, Grunwald M, Ecke GM, et al. The prognosis of mild cognitive impairment in the elderly. J Neural Transm 1998;54(Suppl):31–50.37.)

That's 80% of the patients in this study who did not develop dementia within 3 years of diagnosis.

Currently, there is no way to predict with any certainty which patients with MCI will eventually progress to dementia. Certain "risk factors" have been tentatively identified, but these only mean that a given patient with one or more risk factors is more likely to develop dementia -- they do not mean that a given patient *will* develop dementia. Risk factors that can be measured by clinical tests include atrophy of the medial temporal lobe, certain cerebrospinal fluid biomarkers, APOE4, and neuropsychological markers. More subjective risk factors that have been tentatively suggested include confirmation of memory difficulties by a knowledgeable informant (such as a spouse, child, or close friend), poor performance on objective memory testing, and any changes in the ability to perform daily tasks, such as hobbies or finances, handling emergencies, or attending to one’s personal hygiene.

Now, you may find studies which show a much higher conversion rate than the study conducted by Wolf et al. However, there were some very basic flaws in the way the data was analyzed.

A recent study performed a "meta-analysis", that is, it combined and reanalyzed the results from a number of different studies. The abstract is at: http://jnnp.bmj.com/cgi/content/abstract/79/12/1386.

Basically, what this paper says:

The concept of MCI is only 15 years old, so until recently, it has been impossible to accrue enough prospective data to allow statements on the prognosis to be made with any kind of confidence. The two longest studies published to date both had mean observation periods of 10 years. One reported on subjects with MCI aged 40-85 years who sought help at a memory disorder clinic , and estimated the annual conversion rate to be 4.8%. (This was Visser et al, see below.) The other was based on community subjects (i.e., people who volunteered to be in a study, who were then tested to identify those who had MCI, as opposed to those who had visited a memory disorder clinic complaining of problems.) Of those diagnosed with MCI, 27% developed dementia over the next 10 years, an annual conversion rate of 2.75%. Another 55.0% no longer met criteria for either MCI or dementia within 6 years -- i.e., had reverted to normal.

The largest study looked at members of a religious order (nuns and brothers), of whom 949 had evidence of MCI at baseline. Over an 8 year period, only 7.5% developed dementia (an annual conversion rate of 0.94%) and almost 15% recovered.

The authors looked at the data from 15 long-term studies. The studies had a mean observation period of 6.02 years (range 5.0 to 10.0 years.) Six took place in "specialist clinical settings", and nine were community-based.

Cumulative (not annual) conversion (that is, the percentage of *all* patients who progressed to dementia in the 5-10 years of the studies) was 31.4%.

The authors compared this with the cumulative conversions seen in studies of less than 5 years duration, and came up with 27.4%. Meaning ... (a) the results in the early years were pretty much the same for short-term and long-term studies, and (b) if the patient is going to develop dementia, it is done early on, pretty much within the first 3 years -- the conversion rate drops dramatically in later years.

Across all 15 long-term studies, the mean *annual* conversion rate was 3.3%. The annual conversion rate was higher for studies on patients who sought a diagnosis at a memory disorder clinic -- 6.7% compared to 2.6% for studies done on community subjects.

The authors commented, "We are not the first to suggest that the conversion rate during the first year of observation does not hold linearly thereafter..." and they cited three earlier papers.

The risk factors they discussed were atrophy of the medial temporal lobe, CSF biomarkers, APOE4, and neuropsychological markers. They noted that none of these risk factors would be expected to diminish substantially with time -- rather, the effect of age has been to *increase* the rate at which dementia develops. So why the rapid drop-off in conversion rates? They conclude that patients diagnosed with MCI are a heterogeneous group, who have varying neuropathologies or who have no neuropathology at all. Those with "aggressive" conditions will convert early, leaving a surviving cohort with relatively high resilience. Another possibility is "diagnostic error", i.e., some cases of early dementia are mislabelled as MCI, and these will deteriorate quickly.

Now, they did mention that the conversion rate was "strongly moderated by age" and cited a paper by Visser et al. So I looked up that paper, to get more details.

Visser PJ, Kester A, Jolles J, et al. Ten-year risk of dementia in subjects with mild cognitive impairment. Neurology 2006;67:1201–7. The abstract says, in part:

OBJECTIVE: To investigate the 10-year risk of dementia in subjects with mild cognitive impairment (MCI) ages 40 to 85 years. METHODS: We selected subjects from a memory clinic if they met one of the following definitions of MCI: cognitive complaints (n = 181), aging-associated cognitive decline (AACD) (n = 163), mild functional impairment (n = 86), or amnestic MCI (n = 64). Subjects were reassessed after 2, 5, and 10 years. ...Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years, 55 to 69 years, and 70 to 85 years. RESULTS: The 10-year risk of dementia was 0.27 in subjects with cognitive complaints, 0.28 in subjects with AACD, 0.44 in subjects with mild functional impairment, and 0.48 in subjects with amnestic MCI. ...The risk of dementia increased with increasing age for all MCI definitions (p < 0.001). Depending on the MCI definition used, the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years, from 0.37 to 0.52 in subjects aged 55 to 69 years, and from 0.77 to 1.0 in subjects aged 70 to 85 years. CONCLUSIONS: The majority of subjects with MCI do not progress to dementia at the long term. Age strongly influences the dementia risk. MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects.