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.

Straight Talk: Mild Cognitive Impairment

Contributed by: Dennis Fortier, President, Medical Care Corporation

Mild Cognitive Impairment (MCI) is a term we are seeing more and more frequently in the general press.  Unfortunately, efforts to clarify its meaning often serve to further confuse the issue.

Case in point is a lengthy discussion about MCI, with an associate professor of psychiatry, published recently in the New York Times "New Old Age" blog.  While lots of important ground is covered in the interview, most of the information is geared toward MCI caused by Alzheimer's disease, without proper emphasis and clarity about other, arguably more common causes of MCI.  Population-based studies suggest that prevalence of MCI cases caused by depression, poorly controlled diabetes, sleep-disorders, thyroid conditions, alcohol/drug abuse, medications, and cancer treatments, far exceed the number of cases caused by early stage Alzheimer's disease.

That oversight, that most MCI is caused by common, treatable, medical conditions and not early Alzheimer's disease, undermines the clarity of the piece.  Most of the discussion is geared toward understanding MCI caused by Alzheimer's disease, as opposed to MCI caused by the many other, more common, medical conditions that impair cognition.

This confusion about MCI and the proclivity to attribute MCI to Alzheimer's disease are not new phenomena.  I wrote about it more than three years ago in a post about MCI converting to Alzheimer's disease. In the years since, increased interest in cognitive health has brought increased coverage of these issues.  Unfortunately, much of the coverage is poorly presented and does not aid clarity.

Here is a constructive way to understand the term MCI: While some decline in cognitive function is normal with aging, MCI refers to changes that are more severe than would be expected at a given age, but not so severe as to prevent a self-reliant lifestyle. When cognitive decline is severe enough to prevent self-reliance, we use the term "dementia".  In this way, cognitive health can be viewed as a continuum from "normal aging" to "MCI" to "dementia". One crosses from MCI into dementia when the cognitive decline is severe enough to prevent effective self-care.

Does Nicotine Help Memory?

Contributed by: Dennis Fortier, President, Medical Care Corporation

According to a recent study published in Neurology, there may well be a relationship between memory and nicotine.  But before you run out and take up smoking, let's examine the facts.

First, the study was conducted on a small number of participants (74), all of whom had a mild, prior memory deficit, and the nicotine was delivered through a transdermal patch, not through smoking cigarettes.  After six months, those who had received a nicotine patch outperformed a placebo group on cognitive tests of attention and memory.  In fact, the group receiving nicotine improved their baseline scores while the placebo group showed a decline in thinking abilities over the six month trial.

For sure, the well-documented risks associated with smoking (which include cognitive decline) would preclude any reasonable argument about smoking to preserve brian health.  But nicotine, if delivered without the burden of smoking, has been shown to interact with receptors in the brain and improve some chemical signals along neural circuits. It is more than plausible that this is a benefit we could one day harness for improved cognition.

The major caveats on this particular study are that it was very small, the noted cognitive gains were considered minimal, and many of the authors work for companies that sell nicotine patches.  Nonetheless, this early stage work is noteworthy and bodes well for future benefits.

Memory Loss More Common in Men?

Contributed by: Dennis Fortier, President, Medical Care Corporation

There is much press this week about a study published in Neurology that measured the incidence of mild cognitive impairment (MCI) in an aging population.

MCI is a subtle loss of thinking ability, such as impaired memory or judgment, that is not severe enough to interfere with the person's normal activities of living.  The study showed about a 20% incidence rate which is squarely in line with previous estimates.

The press has been largely focused on the fact that, in this study, men between the ages of 70 and 89 years had a higher incidence of MCI than women of the same age.  This is probably true.  It is also probably easy to explain.

MCI is not a disease, it is merely a descriptor term for a certain level of cognitive impairment.  It refers to the degree of impairment that falls between normal cognition and the severe loss of function that we call dementia.  Asking "why" a person has MCI is a whole different question with a host of common answers including depression, thyroid disease, stroke, sleep disorder, Alzheimer's disease, and anxiety, to name just a few.  

The question of "why" a person has MCI was not adressed in this study, but may shed some important light on the observed gender differences.  For example, sleep disorders and certain cardiovascular conditions, like hypertension and stroke, are common causes of MCI and are somewhat more prevalent among men than women.  Clearly, conditions that impair memory and are also more common in men, could fully explain the observed gender differences in this study.  In that respect, these results are hardly surprising and, in fact, make perfect sense.

It would be truly worthy of a media frenzy if researchers controlled for each cause of MCI and still found that one gender was more susceptible than the other.  But despite many misleading headlines, that was not the case in this study.

How to Read the News: Part 1 of 5

Contributed by: Dennis Fortier, President, Medical Care Corporation
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The purpose of the Brain Today blog is to distill the daily news about brain health and help the public understand the essential meaning of each article. Through time however, I have found myself clarifying the same themes over and over again. Five of these themes are explored in this five-part series “How to Read the News About Alzheimer’s and Dementia”.

How to Read the News About Alzheimer’s and Dementia - Part 1  
Be Aware of the Author’s Definition of Alzheimer’s Disease

A major source of unintended confusion about Alzheimer’s disease (AD) is the inconsistent definition of this disease from one article to the next. In many instances, the author uses a definition that the reader might not fully understand. I explored this problem more fully in an earlier post (When Does Alzheimer’s Disease Really Begin?) but I will summarize it succinctly here.
The problem is that research scientists think about the disease in terms of pathology and speak about it in those terms. Given the long underlying process of amyloid accumulation in the brain, they contend that AD begins decades prior to the first clinical symptoms of memory loss.

Physicians, on the other hand, use a strict clinical definition of the disease stating that AD begins when the underlying pathology (amyloid accumulation) has caused enough brain damage to render the patient demented. In this scenario, the disease begins many years after the first clinical symptoms.

Most lay-people default to a symptom-based understanding and consider the disease present when the symptoms first appear. This occurs at some mid-point between the other two perspectives.

When you read the news, it is important to understand the potential for confusion in this regard. Here are a few of the many examples of how confusion arises:

• If an article says that a drug is useful in treating early-stage AD, you should be careful to understand what the author means by “early-stage”. They might mean "30 years prior to symptoms" or they might mean "the point at which the patient becomes demented". Unfortunately, such claims often breed false hope and are usually not meaningful to those recently diagnosed with AD because, by all definitions, we rarely diagnose the disease early.

• When you read that AD is difficult to distinguish from normal aging, be aware that this is true for some definitions of AD but not for others. There is certainly a clear distinction from normal aging once clinical symptoms appear.

• When you read about mild cognitive impairment (MCI) and that it may or may not convert to AD, don’t be accidentally misled. Focus on any information indicating the cause of the MCI. If it is AD pathology, then scientists would agree that the patient already has the disease while physicians would argue against an AD diagnosis until the symptoms progress to dementia.

Keep in mind these multiple definitions for AD that are commonly used in the press and it will help you to avoid misleading conclusions about otherwise clear news items.

Here are the links to each other part of this series:
Part 2 of 5: Don't be Mislead by Data on Treatment Efficacy
Part 3 of 5: Common Assertions about Diagnostic Accuracy Hide Truth
Part 4 of 5: The Term "Dementia" Cannot be Interpreted Loosely
Part 5 of 5: "No Cure" Not as Bad as it Sounds

When Does Alzheimer's Disease Really Begin?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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When Does Alzheimer's Disease Really Begin?

This question is prone to a wide range of answers because physicians tend to address the question based on a strict, clinical definition of Alzheimer's disease whereas scientists adhere to a different definition. The rest of the world, including journalists, tends to consider the disease more generally. Let me explain.

Consider the intersection of four groups of people who might be involved in a "discussion" about Alzheimer's disease (such as this one recently posted at WebMD). There may be (1) the scientists who study the disease, (2) the physicians who treat the disease, (3) journalists and publishers who glean information from both the scientists and physicians before packaging it for delivery to the public, and (4) the lay-persons who consume all of that information.

There are common discrepancies between how each of these groups thinks about, and in fact define Alzheimer's disease. As such, one group's answer to the question (When Does Alzheimer's Disease Really Begin?) is frequently misinterpreted by a member of another group.

The scientists tend to think in terms of disease pathology. In their minds, as soon as some biological process initiates a cascade of other processes that will eventually lead to Alzheimer's lesions in the brain, then the disease has begun.

The physicians are bound by the duty of consistency to use the definition published and accepted by their peers. Since the clinical definition of Alzheimer's disease currently requires the presence of "dementia", then physicians peg the start of the disease at the point when the patient has accumulated so much brain damage that they can no longer care for themselves without human assistance.

The journalists and publishers are adept at gathering facts and packaging them into public messages. Being unaware of these diverse definitions, they often repeat "expert testimony" without realizing the nuances therein and without clarifying the context of their statements.

The public tends to think about the disease in terms of symptoms. That is, if one has memory loss or other cognitive difficulties, perhaps there is a disease at hand affecting their brain. If one has no symptoms then they are probably in good health. This perspective would consider the start of Alzheimer's to be at the onset of noticeable memory loss. That happens much later than the scientific perspective (biological change not yet manifest in symptoms) but much earlier than the clinical perspective (severe symptoms meeting the definition of dementia).

Here are two common scenarios, both of which lead to confusion.

• A basic scientist might tell a journalist that Alzheimer's disease probably begins thirty years or so before the first symptoms appear. A healthy, lay-person reads the resulting article and worries needlessly about the prospect that they might already have the disease.
• A prominent physician might tell a journalist that patients suffering from memory loss have mild cognitive impairment and may or may not convert to Alzheimer's disease. A lay-person who is clearly in cognitive decline and needs medical attention decides that they may not yet have reached the point where they should seek help.

So what's the answer to the question? It depends on who you ask. The underlying biological changes probably begin decades before early symptoms appear. From the onset of the subtlest symptoms, there is generally a 5-10 year period of mild cognitive impairment during which time an Alzheimer's patient maintains fairly high function and can live independently. This is also considered to be a period when treatment may be optimally beneficial so early detection of symptoms is important. Eventually, the symptoms worsen and the patient becomes demented with an average life expectancy of about 7 years from that point forward.

It really is amazing how much seemingly contradictory information is published about Alzheimer's and dementia each day when, in fact, most of the messages could be well aligned if more care were paid to definitions.

Measuring Brain Volume to Predict Cognitive Decline

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Researchers at the University of California, San Diego have published interesting findings in the journal Alzheimer's Disease and Associated Disorders suggesting that volume measurements computed from MRI images of the brain might be useful for predicting cognitive decline due to Alzheimer's disease (AD).

Their study followed 269 patients with MCI over a six-month period. They analyzed the relationship between tissue volume in three regions of the brain and the patients' scores on neuro-psychological tests. While the relationship between atrophy in one portion of the brain (the hippocampus) and cognitive decline has been suggested for some time, this study demonstrated that useful clinical information can also be drawn from measures of the amygdala and the temporal horn. Taken together, these volumetric measures constitute a useful bio-marker for clinical and research applications in cognitive health.

Using automated, software-driven measures of brain volume, this research suggests that physicians may now have an early clue as to whether or not a particular MCI patient will decline further with Alzheimer's disease. Such knowledge could enable more timely intervention and more effective treatment for AD in the near term.

MCI Correlated with Higher Mortality

Contributed by: Dennis Fortier, President, Medical Care Corporation
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A study recently published in Archives of Neurology shows that individuals with MCI have much greater risk of mortality compared to cognitively healthy individuals.

Robert S. Wilson, PhD, Rush University Medical Center, Chicago, Illinois, and colleagues studied 1,715 older adults, assessed their cognitive status, and measured mortality rates during an ensuing 10-year follow-up period.

"Compared with people without cognitive impairment, risk of death was increased by about 50% among those with mild cognitive impairment and was nearly 3-fold greater among those with Alzheimer's disease", said Wilson

While these results are not surprising, this study is one of the first to show such a clear link between life expectancy and cognitive health.

MCI vs. Dementia vs. Alzheimer's Disease

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Published in the latest issue of The Journal of Family Practice you will find a well-intentioned review article about the Best Practices Identified for Early Alzheimer's Detection.

While I heartily agree with the need to identify and publish standards of care in this field and I applaud the author (Diana Kerwin, MD) for her efforts, this article blurs the important differences between Mild Cognitive Impairment, Dementia, and Alzheimer's Disease. Helping the public to clearly differentiate and fully understand these terms, (as Dr. Kerwin surely does) is one of the main purposes of this blog.

Based on the title of the article, these are best practices for detecting early Alzheimer's disease. Theoretically, this could mean detection in a pre-symptomatic stage or a bit later when the disease has progressed to the MCI stage. However, when detection occurs later than the MCI stage, we are really no longer discussing early stage Alzheimer's but rather mid to late stage Alzheimer's disease. The confusion comes from the fact that mid to late stage Alzheimer's often causes early stage dementia. The terms "Alzheimer's" and "Dementia" are distinct and cannot be (should not be) carelessly interchanged.

On average, Alzheimer's disease begins with a seven year period of mild symptoms prior to a patient becoming demented. As such, mid to late stage Alzheimer's is usually contemporaneous with early stage dementia. Switching carelessly between the terms breeds unnecessary confusion.

As a final note, the author also included a list of "optimal screening tests and tools to prevent delayed diagnosis of mild-to-moderate dementia patients" which I contend perpetrates somewhat of a false frame. Patients who are mild to moderately demented have a cognitive deficit severe enough so as to be obvious to a caregiver or physician. These patients can no longer care for themselves and no screening tests or tools are necessary to detect the problem. Truly beneficial tests and tools are those that distinguish more subtle impairment from normal declines due to healthy aging.

How to tell if MCI will convert to Alzheimer's Disease?

Contributed by: Dennis Fortier, President, Medical Care Corporation
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I commonly encounter this question in the press, I hear it discussed at conferences, and physicians pose it to me on a regular basis. Despite the centrality of this question in so many forums of cognitive health, it is a nonsensical inquiry with inherent flaws. Additionally, it propagates a pernicious brand of confusion that I want to clarify today.

As per my earlier post, Mild Cognitive Impairment 101, there are many medical conditions that can cause a subtle cognitive deficit. Pondering whether or not MCI will "convert" to Alzheimer's Disease (AD) obscures the fact that MCI is a symptom of an underlying medical problem (not the problem itself). In fact, some MCI is actually caused by AD and therefore, the prospect of converting does not belong in a logical, informed discussion.

When MCI is present, the correct question is "what is the cause of the impairment?". If the answer is AD, then the folly of a conversion outcome is clear; the disease precedes the impairment and not vice-versa. If the MCI is caused by some other medical condition (depression, vascular disease, anxiety, etc.) then it is equally futile to consider whether or not it will convert to AD; these medical problems are separate and distinct. That is not to say that such a particular person will never get AD because they may. In fact, the medical condition causing their impairment might even confer a greater risk for AD, but the notion of "converting" from MCI to AD is illogical.

A good analogy would be to learn of a patient with excessive thirst and blurry vision and then wondering if these symptoms will ever "convert" to Diabetes. Most physicians would perform a diagnostic work-up, take note of the high blood sugar, and diagnose diabetes immediately. There would be no debate about whether or not the symptoms would covert to the disease -- they would conclude that the presence of the disease has caused the symptoms. We must do the same with MCI. That is, perform a work-up and identify the underlying cause of the symptoms so that the patient may benefit from timely intervention.

So why have I labeled this as "a pernicious brand of confusion"? Because the perpetration of the idea that MCI might or might not convert to AD prevents some (if not many) primary care physicians from proactively diagnosing the cause of MCI and treating it. Giving any credence to the notion that MCI is a sporadically progressive precursor to AD is a barrier to clarity and interferes with a higher standard of care in this field.

Mild Cognitive Impairment 101

Contributed by: Dennis Fortier, President, Medical Care Corporation
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Mild Cognitive Impairment (MCI) is now widely but inconsistently used to describe a broad range of cognitive states. While there may not yet be a universally accepted definition, there is adequate consensus that MCI describes the space on the cognitive continuum between "Normal" and "Demented". Recall from an earlier post (Dementia 101) that a person does not meet the clinical definition of dementia until their impairment is severe enough to interfere with their social or occupational function. From this definition, the need arose to describe the situation when a person is beginning to lose function but the deficits are still subtle and not yet severe enough to meet the criteria for "dementia". To address that need, researchers at the Mayo Clinic constructed the term Mild Cognitive Impairment which has been quickly, if not uniformly, adopted in the scientific community.

As with dementia, Mild Cognitive Impairment is not a diagnosis and not something that must be treated. It is merely a symptom of some underlying medical condition such as depression, Parkinson's Disease, Vitamin B-12 deficiency, early stage Alzheimer's Disease, etc.

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