Improving our Ability to Make a Diagnosis
Some of our research is focused on efforts to improve our ability to make a confident diagnosis as early as possible. Early diagnosis is essential if we ultimately want to try to treat these conditions while people are still only mildly symptomatic. We were involved in the development of diagnostic criteria for behavioral variant Frontotemporal Dementia and Posterior Cortical Atrophy. We have also guided the field’s overall thinking about how to formulate a patient’s diagnosis including information about their symptoms as well as information about the likely underlying brain condition that is causing those symptoms. We call this the 3-step diagnostic formulation. We have also contributed to the field’s knowledge about the use of advanced brain imaging techniques, including MRI and PET scans, to help understand each patient’s diagnosis. We have helped bring some of these methods and technologies into the clinic for practical use with patients and others are still being studied in research to see if they will be helpful.
Diagnostic terminology in the field of neurodegenerative dementias can be confusing—to health care professionals as well as laypeople—because it sometimes refers to the clinical syndrome (a patient’s symptoms), or to the brain disease causing the symptoms, or sometimes to both. This terminology is evolving partly because we have begun to be able to measure “biomarkers” of the brain disease(s) in living people. As an example, previous diagnostic criteria for dementia required memory loss, but it is now recognized that dementia is an acquired cognitive or behavioral impairment that might initially affect domains other than memory (e.g., language, visual or spatial abilities, social abilities). As another example, prior clinical diagnostic criteria for Alzheimer’s disease (AD) required that patients have dementia with memory loss in order for a diagnosis to be made, but contemporary criteria acknowledge that there are a variety of types of symptoms that may be the first evidence that a person has AD in the brain. Furthermore, with contemporary biomarkers, it is possible to identify evidence of neuritic plaques and neurofibrillary tangles—the two major types of brain pathologic changes in AD—in living people with Mild Cognitive Impairment (MCI), prior to dementia, and even in people who are completely normal in terms of brain function. Some of our and others’ studies have shown that brain changes associated with AD or related diseases may be detectable 10 or even 15 years (or possibly longer) prior to any symptoms being present.
In an attempt to organize all of this information, we have developed a three-step diagnostic formulation in cases of suspected neurodegenerative cognitive impairment. The first step denotes a patient’s overall Cognitive Functional Status as one of normal cognition, subjective cognitive decline, MCI, or mild dementia, moderate dementia, or severe dementia. The determination of Cognitive Functional Status is based on a clinical judgment regarding the impact of symptoms on a patient’s ability to carry out usual activities in daily life independently.
The second step aims to determine whether the patient’s symptoms and signs match a recognized Cognitive-Behavioral Syndrome, such as a primary amnesic syndrome (memory loss), Primary Progressive Aphasia (language impairment), a primary dysexecutive syndrome (difficulty with organizational and problem-solving abilities), a primary visual or spatial syndrome (often referred to as the Posterior Cortical Atrophy syndrome), the behavioral variant frontotemporal dementia syndrome, Corticobasal Syndrome (motor control), or others. The determination of Cognitive-Behavioral Syndrome is based on a clinical judgment integrating information reported by the patient and care partner about symptoms, the clinicians’ observations about the patient’s behavior during the interview and examination, and the patient’s ability to perform tests of thinking abilities.
The third step aims to establish the likely brain disease or condition causing the clinical syndrome. Some Cognitive-Behavioral Syndromes are more likely to be caused by certain diseases, so this determination integrates this information about the probability that a particular Cognitive-Behavioral Syndrome is usually caused by a specific brain disease or condition, along with brain imaging, laboratory tests and/or biomarker tests.
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