This transcript has been edited for clarity.
Today we’re going to discuss a new clinical practice guideline from the Alzheimer’s Association on the evaluation and testing for Alzheimer’s and related dementias. This is an important area for us in primary care because we are the first clinicians that most patients see when they are concerned they may be having memory problems or dementia symptoms. It’s a challenging area and this document provides much-needed guidance.
The Alzheimer’s Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer’s Disease and Related Disorders (DETeCD-ADRD) recommends a three-step approach to diagnosis. The first step is to assess whether there’s a cognitive deficit. If there is a cognitive deficit, then assess whether that deficit fits mild cognitive impairment (MCI) or whether it fits mild, moderate, or severe dementia. Remember the main difference between MCI and dementia is that dementia, by definition, interferes with the capacity for independent everyday activities.
It’s important to get a history from both the patient and a significant other, with attention to activities of daily living, time course of the cognitive decline, and any potential precipitating factors. Patients themselves may not always give the best personal history to provide a complete picture of what’s going on, due to factors such as memory impairment, embarrassment, or a lack of self-awareness. In addition, the DETeCD-ADRD guideline recommends performing a mental status exam using a validated instrument like the Montreal Cognitive Assessment or the Mini Mental State Examination. If that evaluation shows that the patient is cognitively unimpaired, then no further evaluation is needed and we can educate the patient about brain healthy behaviors and, of course, plan for follow-up assessment. If the patient does show evidence of cognitive impairment, then it’s important to define the effect of that impairment on the patient’s function.
The second step in the evaluation is to characterize the clinical profile of a patient’s cognitive-behavioral syndrome. What this means is that we want — to the degree that is reasonable — to delineate the domains of impairment, which might include memory, executive function, attention, language, and emotional and social functioning. Here’s where neuropsychological testing can be helpful, if it’s available. These first two steps allow us to develop a plan for personalized care and support.
The third step is testing to help figure out the cause of the patient’s symptoms. It’s important to differentiate Alzheimer’s disease from Alzheimer’s disease–related dementias (ADRD), such as frontotemporal dementia, Lewy body dementia, multi-infarct or vascular dementia, or mixed vascular and Alzheimer’s dementia. It’s also important to determine if the cognitive decline is caused by or being made worse by other diseases like depression, sleep apnea, and B12 deficiency or if other factors like the effect of medications (eg, anticholinergics and alcohol) are contributing to the cognitive or behavioral symptoms.
Step 3 of the evaluation includes ordering what the guidelines refer to as “tier 1 laboratory studies.” They are first tier because these are laboratory studies that are considered routine and should be ordered for all patients who have MCI or dementia. The recommended labs should include a complete blood cell count with differential, complete metabolic panel, erythrocyte sedimentation rate, and tests for thyroid-stimulating hormone, vitamin B12, homocysteine, and C-reactive protein levels. In addition, the DETeCD-ADRD guideline recommends that physicians order imaging, preferably a brain MRI without gadolinium or, if MRI is contraindicated, a noncontrast head CT. The MRI can rule out tumor, show multiple infarcts, or show regional atrophy patterns that may suggest specific neurodegenerative pathologic changes — but it’s important to recognize that the MRI is not in any way diagnostic.
The guideline recommends against using the term “labs for reversible causes of dementia” because the labs only rarely uncover a cause for dementia that is reversible. The guideline authors cite a meta-analysis that showed less than 1% of dementia syndromes are reversible, but nearly 10% of people with dementia have a common comorbid condition that may be contributing to their decrement in cognitive function. This certainly fits my experience. The preferred term for tier 1 labs is a “cognitive lab panel.” Additional testing, termed tier 2 and 3 tests, are only recommended when necessary on an individual basis. These can include sleep studies and antinuclear antibody, folate, ammonia, lead, Lyme antibody, rapid plasma reagin, and HIV tests. Of course, there are plenty more tests that can be done in specific circumstances.
Now what’s missing here? How about blood biomarkers for Alzheimer’s disease? I recently reviewed the Alzheimer’s Association workgroup recommendations on revised criteria for diagnosis and staging of Alzheimer’s disease. The key principle which that guideline lays out is that Alzheimer’s disease is defined by its biology — neuropathologic changes in the brain, like deposition of amyloid and tau protein. We are now on the cusp of having blood-based biomarkers for amyloid beta and p-tau that will enable us to either rule in or rule out Alzheimer’s disease with a high degree of accuracy. It’s important to recognize that while the biomarkers are promising and will be incredibly useful, they still need to be further validated in large populations. And although the blood biomarkers can now be ordered through many lab tests, there is not yet a biomarker that is fully approved by the US Food and Drug Administration. In my opinion, start to understand the place of blood biomarkers now, because once they are regulatory approved, they’ll become a routine addition to the initial panel of laboratory tests that we typically order when evaluating patients for dementia.
Finally, I was thrilled to see that the guidelines specifically acknowledge that in the primary care setting, two or more problem-focused visits would usually be required to assess for dementia. I certainly find that to be the case. When there’s uncertainty with regard to diagnosis, early age of onset, rapid progression, and/or consideration of biologic therapy, then referral to a dementia specialist makes sense.
This is an important update and it provides a clear, straightforward approach which allows us to evaluate patients for dementia with confidence. I’m interested in your thoughts, please leave them in the comments section below. For Medscape, I’m Dr Neil Skolnik.
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