SAGE: A short test for detecting Alzheimer's?


Contributed by: Dennis Fortier, President, Medical Care Corporation
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The Self-Administered Gerocognitive Examination (SAGE) has received a fair amount of attention this year. Most of the attention has been driven by PR efforts and a website hosted by The Ohio State University where the test was developed.

Unfortunately, much of the press coverage has been somewhat sloppy and perhaps misleading. While the scientists who developed SAGE described it as "a test to measure thinking abilities", the press has repeatedly characterized it as an Alzheimer's test. As readers of this blog know, dozens of medical conditions can impair memory and other thinking abilities, Alzheimer's disease is merely one of them.

Press mis-characterizations aside, the data supporting the validity of the SAGE is quite minimal.  The instrument, a 15-minute self-administered questionnaire, was developed based on responses from a small sample of 63 subjects, and then validated on a sample of 1,047 subjects.

The website and support materials for the SAGE suggest that the instrument can detect dementia with fairly high accuracy of 95%. This has been the root claim for much of the ensuing press coverage. Remember though, the definition of dementia includes "impairment severe enough to interfere with social and occupational function". In this regard, a test that can detect such severe impairment may have little value, especially if it cannot detect more subtle symptoms such as those we see in the earliest stages of Alzheimer's disease.

From a clinical point of view, it is much more important to detect subtle stages of decline called Mild Cognitive Impairment (MCI). MCI is caused by a great many medical conditions and is often confused with normal, age-related changes in cognition. In fact, incorrectly assuming that subtle changes are caused by normal aging, rather than by an emerging medical condition, is the primary foe in our efforts to intervene at early stages against the various conditions that impair memory. Distinguishing the two is key to proactive management of cognitive health. According to the instrument's website, the SAGE is 62% sensitive for detecting MCI, which will provide little help for physicians trying to distinguish MCI from normal aging.

Other well-validated instruments are more useful in detecting MCI.  The most accurate test in the published literature is the MCI Screen.  It is 97% accurate in distinguishing MCI from normal aging, but it is not self-administered. Rather, it is generally administered by medical staff or a researcher. The ideal would be an instrument with the self-administering ease of the SAGE and the accuracy of the MCI Screen.

Is the Risk for Alzheimer's Disease Declining?



Contributed by: Dennis Fortier, President, Medical Care Corporation
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Stop the press! Is this good news about Alzheimer's Disease? It depends on how you look at it.

A recent perspective article*, published in the New England Journal of Medicine, cites several studies supporting the notion that the risk of having Alzheimer's disease is declining. The article notes that the probability of a person of a given age, having any form of dementia today, is lower than it was a few decades ago. That sounds positive.

Despite the tempting headline of "Declining Risk", such a trend is most likely driven by overall improvements in population health. Today's seniors are unquestionably wealthier and better educated than those of the past, they smoke less, have fewer strokes, have better managed cholesterol, and have lower blood pressure. All of those factors affect risk of Alzheimer's disease and other causes of dementia.

Also, while risk at a given age may be declining, the number of people reaching old age (and even very old age) is sharply climbing. Prevalence at a given age may be lower, but incidence at older ages is clearly rising.

There is no reason to believe that the risk of Alzheimer's disease is magically declining. There is much hope, however, that awareness about risk factors and the importance of managing them, is helping us to forestall the ravages of dementing illnesses, and buying time for the nation's R&D efforts to find better treatments.

So keep exercising, eating right, using your brains, and managing your chronic conditions.  For now, that is your best strategy for keeping your brain healthy for the longest time.

n engl j med, 369;24, nejm.org, december 122013

Screening for Cognitive Impairment

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Yesterday, the U.S. Preventative Services Task Force (USPSTF) ruled that there is insufficient evidence to make a recommendation, either for or against, routine screening for cognitive impairment in older adults. Today, the press is ablaze with sloppy reporting on the matter.

Many news stories (like this from US News and World Report) are conflating cognitive impairment with dementia, but readers of this blog understand that cognitive impairment may be very mild whereas dementia is, by definition  a severe loss of cognitive capacity. Many others (like this from Time), are interchanging dementia and Alzheimer's disease, which inappropriately implies that the two are one in the same, and obscures the fact that Alzheimer's is but one of the many causes of dementia.

To be clear, the USPSTF did not rule against anything. They merely concluded that the evidence is not strong enough to make a recommendation one way or the other. More importantly, their ruling was related to "screening" of "older adults" for "cognitive impairment". In other words, should the healthcare system invest in regular cognitive assessment of all older adults, whether they suspect a problem or not? Their conclusion? They're not sure.  They're not for it and not against it.

Rather, the public should monitor their cognitive health vigilantly and promptly report concerns to their physicians for a thorough evaluation. This will allow early intervention against treatable problems like thyroid dysfunction, vitamin deficiency, anxiety/depression, sleep disorders, and out of control diabetes, all known contributors to cognitive deficits. It will also facilitate early diagnosis of Alzheimer's disease.

This is important because Alzheimer's can be effectively managed for a significant percentage of patients. Effective management of Alzheimer's includes early diagnosis, physical exercise, proper diet, strict control of hypertension and diabetes, poly-therapy with a cholinesterase inhibitor and Namenda, ongoing social and intellectual stimulation, and caregiver education. All of these interventions have been shown to promote optimal disease management and, when brought together as a robust therapeutic regimen, can be surprisingly effective.

Time to Redefine Alzheimer's Disease


Contributed by: Dennis Fortier, President, Medical Care Corporation
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Daily news stories abound with coverage of new treatments and diagnostic tests for Alzheimer's disease.  Many include controversial musings about the value of measuring risks or "predicting" future diagnoses.  Most of these discussions are poorly informed, and further limited in their usefulness by a lack of agreement about the definition of Alzheimer's disease.  After all, detecting the disease "early" is a relative concept, completely dependent on your definition of when it begins.

As we wrote earlier in a post about when Alzheimer's disease really begins, there are wide disparities in the opinions of scientists, clinicians, patients, and journalists.  The scientists look at pathological changes prior to symtoms, the clinicians adhere to a strict definition that includes severe symptoms, patients define it's onset in accordance with minor symptoms, and journalists, often unaware of these nuances, frequently muddy the waters with inadvertent generalizations.

There is strong rationale, in terms of promoting proactive healthcare and enabling an aggressive research agenda to develop better treatments, in favor of universally adopting a definition based on known pathological changes that occur early in the disease process. Doing so would peg the start of the disease at an early time, prior to the development of clinical symptoms.  This approach, with which we agree, is highlighted in a clear and objective report from NPR today.

Much Ado About Blood Test for Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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The general press is widely reporting today on a blood test for predicting Alzheimer's Disease (AD). The media coverage is based on a study conducted at Georgetown University Medical Center and published in Nature Medicine. Despite the intense focus, there really may be very little news in this story.

It is unclear why CNN would report this as a "first-of-its-kind" study, when dozens of such studies have been presented and published over the last decade (we wrote in this space about one from Johns Hopkins and another from Scripps). Past studies have been based on various, different elements in the blood but have, in some instances, shown similar levels of predictive accuracy. This study was certainly among the most accurate, but even these results need to be considered in the context of how AD progresses

In terms of AD progression, there seems to be a fairly low level of appreciation, among health reporters, about the underlying nature of the disease. To suggest that we can somehow predict sudden and stark symptoms that mark the beginning of AD, is to ignore decades of research showing that pathological changes associated with the most common forms of the disease, progress slowly for decades before damaging the brain enough to produce symptoms. At best, this new blood test might give insight that a person is in that long, variable process. But bear in mind, autopsy data show that nearly everyone has AD pathology in the brain after age 65, though most do not have any AD symptoms. Therefore, a test to detect what we currently believe to be the pathology, just isn't yet very informative.

Furthermore, a new blood test that suggests those pathological changes are underway is great, but physicians can already detect such murky signs in many ways (MRI scan, spinal tap, PET Scan, etc.). Blood tests have general advantages in terms of cost and convenience, so the reported accuracy of this test is certainly a welcome step forward. But it probably doesn't provide a lot of new insight about whether or not  a person is progressing toward the symptomatic stage of AD.

Finally, the fervor from the ethicists about the moral dilemmas associated with AD diagnoses, is misplaced. If some society wants to make a universal decision about whether or not every citizen should or should not have access to such tests, then the ethicists should weigh in. In our society, where people can decide for themselves if they wish to see a doctor and complain about a symptom, there really is no moral dilemma: those who want information will seek out such tests, and those who do not, will not.