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New Ways to Diagnose Alzheimer’s Disease

Over the past 25 years there have been few changes in the diagnosis of Alzheimer disease (AD) even though our knowledge of the disease and its progression has grown. For example, the current criteria have age cutoffs (between 40 and 90 years of age), but we know now that many people living into their 90’s are at risk for AD. Also, the current criteria do not include use of supporting information from genetic studies or biomarker results. Recent research has drawn attention to using images of the brain and of the hippocampus (the place in the brain where memory consolidation occurs) to measure changes that may mark the early stages of the disease.

New criteria have been proposed to integrate the biological and epidemiological information we now have. The diagnosis of “all cause dementia” is similar to the current diagnosis in that it focuses on problems in social or occupational function (i.e. every day activities), that are a clear decline from a previous level and are due to cognitive loss. However, unlike current criteria for dementia, memory impairment may be apparent, but is not required. The criteria for the clinical diagnosis of the specific condition of Alzheimer disease also includes gradual onset of problems. Probable AD would be defined by evidence of clinical decline which means worsening noticeable by families or doctors. However, if this type of information is not available, (such as when there is no way to be sure about the previous ability), biomarkers including genetic markers could provide support for the diagnosis. This approach suggests that we have growing confidence in biomarkers (such as brain scans) as an indicator of specific disease.

Diagnostic criteria were also proposed for symptomatic predementia known as Mild Cognitive Impairment (MCI), consisting of 4 basic elements: 1) Concern about any cognitive change, not just memory; 2) poor performance in any cognitive area including but not exclusively memory; 3) relatively normal day to day function and 4) the absence of dementia. MCI cases could be evaluated for the etiology (cause) of the problem and the likelihood of AD might be determined by the type of cognitive problem (such as memory loss), or by genetic (such as Apolipoprotein E4 ) and biomarker data that are strongly associated with AD diagnosis.

Perhaps most controversial is the attempt to define a “pre-clinical” Alzheimer disease. This asymptomatic (normal) condition would be defined by biomarkers associated with AD pathology in the absence of any clinical features. While this may be a step toward earlier detection of AD, more information is needed before we can confirm that biomarkers in AD are really predictive of specific conditions when there are no symptoms present. Currently, markers thought to indicate AD have been present in about a third of the elderly asymptomatic individuals and right now we have no evidence that these people get worse. This highlights the importance of following normal volunteer elders to determine if we can accurately predict the onset of AD.


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