Predicting Who Gets Alzheimer's Disease Using Mild Cognitive Impairment Tests
In the past few years, there has been a great deal of new research that has been
focused on predicting who will eventually develop alzheimer's disease.
The new research has focused on a concept called MCI, mild cognitive impairment. Basically, research has been
looking at elderly people who are relatively normal but have some mild memory problems to see what factors in their
history make them later develop alzheimer's disease. If people can be identified before they
develop alzheimer's disease, drugs and other new therapies may delay the progression to full
blown alzheimer's disease.... at least that is the hope of the new research.
There are specific guidelines that are used to decide if someone has mild
cognitive impairment. First, the person with suspected MCI must feel that they have problems with
memory. In addition, family and friends also see evidence of memory loss as they relate to that
person during every day life. A person with MCI doesn't have problems with thinking, speech or
problems doing routine financial things, such as writing checks. Persons with MCI also have full ability to
manage their daily activities of daily living, such as bathing, dressing and eating. The last guideline for
MCI diagnosis is that the person has no other medical, neurologic or psychiatric illness to account for the
subjective memory loss.
The diagnosis of MCI has been very useful to date. It has been found that
among people who meet the guidelines for MCI, almost 50 percent will eventually develop
alzheimer's disease within 3 to 5 years[1]. Still, not everyone with MCI develops alzheimer's
disease. One study found that 25 percent of MCI cases do not progress to alzheimer's disease,
even after 10 years of memory problems [2]. Of those MCI cases who do
progress to alzheimer's disease, more than 60 percent have a history of depressive illness
along with memory impairment[3]. A history of depressive illness significantly increases the risk for
alzheimer's disease. A more comprehensive look at depression as a risk factor for alzheimer's disease
can be found by clicking this link.
Depression And Alzheimer's Disease.
The most useful way of diagnosing MCI is to ask the person directly if they have
memory difficulties (called self-reported memory loss) or to ask friends and family if the person they live
with has memory difficulties (called informant-reported memory loss). A new test, called the
Alzheimer's Questionnaire (AQ), has been successfuly used to diagnose MCI. The test is given by
a physician in the office and involves asking friends and family about memory loss in their loved one.
The test diagnoses MCI with 94 percent specificity [4]. A recent study found that
four questions on the AQ best predict who has MCI [5]...
- Does your relative repeat statements and or questions often?
- Does your relative have trouble knowing the day, date, month, year or time?
- Does your relative have difficulty with managing finances?
- Does your relative have a decreased sense of direction?
Weight loss may be an additional indicator of who develops alzheimer's disease.
A large number of people were followed from 1972 to 1993 in the Rancho Bernardo Study [6].
This study found that people who developed alzheimer's disease lost weight before they were
diagnosed with the disease. Comparable elderly people who remained free of alzheimer's disease never lost
weight, but remained stable or gained weight. Another study found that an acceleration of weight loss in an elderly
person is also linked to developing alzheimer's disease earlier on [7]. Another study found that
patients who develop alzheimer's disease have already lost a significant amount of weight 4 to 6 years
before they are diagnosed with alzheimer's disease [8]. My father was diagnosed in 1990 with alzheimer's disease,
but the year before he was diagnosed, he lost more than 30 pounds, despite being healthy and eating normally. For
my dad, weight loss was the earliest sign of alzheimer's disease, even before he developed memory problems. The reason
for early weight loss in patients who later develop alzheimer's disease is not yet known.
There have been many studies using biomarkers to predict when MCI converts to
alzheimer's disease. MRI scans have been done on people with MCI, and those MCI patients who later
develop alzheimer's disease tend to have reduced brain areas in the hippocampus, an area of the brain
important to memory [9]. The trouble with MRI scans is that they are only partially predictive of
MCI conversion to alzheimer's disease. A master study has found that reports of memory complaints are better
predictors than MRI scans of who goes on to develop alzheimer's disease [10].
An interesting new biomarker for MCI conversion to alzheimer's disease has been found by
checking cerebrospinal fluid. People who have MCI and later develop alzheimer's disease tend to have
reduced levels of amyloid beta and increased levels of phosphorylated tau in their spinal fluids. More than
100 studies have validated this finding. The combination of the two indicators successfully identifies
those without alzheimer's disease from those with alzheimer's disease with 85 percent accuracy.
The combination of the two indicators in spinal fluid successfully predicts, with 90 percent
accuracy, persons with MCI who later develop alzheimer's disease [11].
References
1. Grundman,M.et.al.,ADCS Cooperative Study. Rate of dementia of the alzheimer type in subjects
with mild cognitive impairment.Neurology, 1996, 46: A403
2. Chertkow,H.et.al.,Predicting progression to dementia in elderly subjects with mild cognitive
impairment- a multidiscplinary approach. 2001 Contemporary Clinical Issues Plenary Session. 53rd
Annual Meeting American Academy Of Neurology, Philadelphia, 2001.
3. Visser, P.et.al.,Distinction between preclinical alzheimer's disease and depression.
Journal of the American Geriatric Society, 2000, 48: 479-484.
4. Sabbagh,M.N., et.al.,The Alzheimer's Questionnaire: A proof of concept study for a new
informant-based dementia assessment. J Alzheimers Dis.,2010, 22: 1015-1022.
5. Malek-Ahmadi,M., et.al., Informant-reported cognitive symptoms that predict amnestic mild
cognitive impairment. BMC Geriatr., 2012, 12:3, doi: 10.1186/1471-2318-12-3.
6. Barrett-Connor,E.,et.al.,Weight loss precedes dementia in community-dwelling older adults.
J. Am. Geriatr. Soc.,1996, 44, 1147-1152.
7. Johnson,D.K.,et.al.,Accelerated weight loss may precede diagnosis in alzheimer disease.
Arch. Neurol., 2006, 63, 1312-1317.
8. Morris,J.C.,et.al., Pathologic correlates of nondemented aging, mild cognitive impairment
and early- stage alzheimer's disease. J. Mol. Neurosci., 2001,17, 101-118.
9. Devanand,D.P.,et.al., Hippocampal and entorhinal atrophy in mild cognitive impairment:
prediction of alzheimer disease. Neurology, 2007, 68:11, 828-836.
10. Schmand,B., et.al., Meta analysis of CSF and MRI biomarkers for detecting preclinical
alzheimer's disease. Psychol. Med., 2010, 40:1, 134-145.
11. Hansson, O.,et.al., Association between CSF biomarkers and incipient alzheimer's disease in
patients with mild cognitive impairment: a follow-up study. Lancet Neurol., 2006, 5, 228-234.