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Visualizing the Progression of Alzheimer’s Disease

Changes in thinking or memory ability are common with aging. Some of these changes are curable and some are not, but a patient’s care, management, support and preparation are all improved by having a more accurate diagnosis. At CTIPM, we seek to provide the most complete description of brain anatomy available to guide our referring physicians toward an accurate diagnosis at the patient’s first note of concern.

One unfortunately common cause of memory complaints in the elderly is Alzheimer’s disease, which afflicts more than 40 percent of individuals over age 85. Alzheimer’s is a devastating neurodegenerative disease that impairs memory and cognition as neurological connections are lost and brain tissue atrophies. Alzheimer’s begins to damage brain structures years before most patients notice any change in memory, and this damage can be evident in images of the brain. Medical imaging assists physicians to diagnose the disease, track its progression, and evaluate how well new therapies are working work to slow its advance.

CTIPM employs magnetic resonance imaging (MRI) of the brain and other imaging technologies, as well as sophisticated post processing of obtained images, to quantitatively assess whether and how much the disease has advanced in various parts of the brain.

In one recent case, a 73-year-old patient complaining of memory problems came to UC San Diego for assessment. The patient underwent a specialized MRI exam, and the resulting images were processed by CTIPM so that physicians could evaluate brain damage through an analysis called “Quantitative Segmental Volume Assessment.” The initial MRI exam showed lower-than-expected volumes of the brain’s memory structures (left image, in yellow). Two years later, the same patient was imaged again (right image).

Images from a 73-year-old patient complaining of memory problems

MRI brain memory structure

CTIPM’s ability to register one image with the other and provide analyses of precisely the same segments of the brain allowed the radiologist to view and assess the exact same slice position, regardless of head positioning. The result was a detailed view of change over time. The images above clearly revealed an ongoing neurodegenerative process, and this patient was subsequently enrolled in a clinical trial of a new Alzheimer’s disease therapeutic.

Quantitative, segmented measurements of brain volume offer physicians a more precise assessment of the condition of an Alzheimer’s patient, as compared to conventional qualitative assessments by radiologists, which are often in the form of one or two-paragraph interpretive descriptions of what the images show.

“What we’re collecting is a series of measurements of brain volume, which allows the clinician to see if the patient’s brain anatomy appears normal or deviating from normal,” says Dr. James Brewer, co-director of Neurology & Neuro-Imaging at CTIPM. “Our goal is to empower the referring physician to have this kind of quantitative information, which they can then use in their overall evaluation of the patient.”

Other UC San Diego advances in brain imaging for Alzheimer’s disease have included the combination of MRI exams with positron emission tomography (PET) scans. For PET scans, a slightly radioactive tracer is injected into the patient, and this tracer binds to a protein called amyloid, the presence of which is a hallmark of Alzheimer’s disease. Studies of patients with Down Syndrome, who have a much higher incidence of Alzheimer’s than the general population, suggest that a particular gene may play a protective role in removing the amyloid proteins.

Other recent developments include the development of another radioactive tracer for use in PET scans. This tracer binds to tau, a second protein seen in the brain in the presence of Alzheimer’s disease.

“The ability to directly image all of these markers in the brain has been powerful for clinical trials, and the translation to clinical practice is tremendously exciting,” says Brewer. “Improving diagnosis in the clinical setting will not only improve patient management on a larger scale, but it will circle back to support the development and testing of new therapeutics as physicians get better at detecting earlier who has the disease and who doesn’t, and, further, how the disease expresses itself differently in different populations and genetic backgrounds.”