Positron Emission Tomography (PET) scanning is a powerful tool for detecting and characterizing neurodegenerative diseases. While dementia is a broad term describing cognitive and behavioral symptoms, PET scans offer a unique window into the underlying biological changes in the brain. By visualizing specific molecular and metabolic processes, this technology moves beyond imaging the brain’s structure. This allows physicians to detect disease hallmarks that are often present long before major cognitive decline is clinically apparent, aiding in confirming a diagnosis and distinguishing between various types of dementia.
How PET Scans Image Brain Activity
PET differs from structural imaging modalities like Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), which capture the physical shape and size of brain tissue. The PET technique is a form of functional imaging, designed to measure cellular activity, such as metabolism or protein accumulation, rather than anatomy. This measurement is achieved by injecting a small amount of a radioactive substance, known as a radiotracer, into the bloodstream.
Once injected, the radiotracer travels to the brain and accumulates in tissues based on the specific biological process it targets. The radioisotope component emits positrons, which collide with electrons, resulting in the annihilation of both particles. This collision produces two gamma rays that shoot out in opposite directions.
The PET scanner, a ring of detectors surrounding the patient, senses these paired gamma rays simultaneously. A computer system uses the location and timing of these events to reconstruct a three-dimensional image of the tracer’s distribution. Areas of the brain with higher cellular activity accumulate more tracer and appear brighter, providing a map of the brain’s function at a molecular level.
Identifying Specific Dementia Biomarkers
The specificity of PET imaging in dementia relies on using different radiotracers, each designed to bind to a distinct biological marker associated with neurodegeneration. The most commonly used tracers target either cellular metabolism or the abnormal protein deposits characteristic of these diseases.
One established application is FDG-PET, which uses a glucose analog ($\text{}^{18}$F-FDG) to map the brain’s consumption of sugar. Because neurons rely heavily on glucose, reduced uptake (hypometabolism) in specific brain regions suggests neuronal dysfunction or loss. A characteristic pattern for Alzheimer’s disease (AD) is bilateral hypometabolism in the posterior cingulate, precuneus, and temporoparietal lobes. This pattern is distinct from other dementias, such as Frontotemporal Dementia (FTD), which typically shows hypometabolism localized to the frontal and anterior temporal lobes.
Beyond metabolism, other tracers directly target the abnormal proteins that accumulate in the brain. Amyloid PET uses tracers that bind specifically to beta-amyloid plaques, one of the pathological hallmarks of AD. A positive amyloid scan confirms the presence of this protein deposit in the cerebral cortex, which is a necessary biological criterion for an AD diagnosis. However, amyloid deposition can occur years before the onset of cognitive symptoms, and the total amyloid burden does not strongly correlate with the severity of current cognitive decline.
The second core protein involved in AD is tau, which aggregates into neurofibrillary tangles inside neurons. Tau PET utilizes tracers to bind to these tangles, showing the topographical spread of tau pathology. Unlike amyloid, the concentration and spread of tau tangles correlate more closely with the degree of neurodegeneration and the severity of cognitive impairment. The combined use of amyloid and tau PET provides a comprehensive view of the disease process, with amyloid confirming the underlying pathology and tau indicating its progression.
Integrating PET Results into Diagnosis
PET scan results are rarely used as a standalone diagnostic tool, instead serving as a biomarker to support clinical assessments, neurological exams, and other imaging. The primary role of PET imaging is in differential diagnosis, especially when the cause of cognitive impairment is unclear. The distinct metabolic patterns shown by FDG-PET help differentiate between AD, FTD, and Dementia with Lewy Bodies (DLB), which often presents with a unique pattern of hypometabolism in the occipital cortex.
PET imaging is also valuable for distinguishing true neurodegenerative disease from conditions that mimic dementia, often called pseudo-dementia. Cognitive impairment caused by severe depression or other psychiatric conditions may yield an FDG-PET scan that is normal or shows a different pattern of frontal hypometabolism. A normal FDG-PET scan makes a diagnosis of AD very unlikely.
A positive PET result for a protein biomarker does not automatically confirm a symptomatic diagnosis. For example, a positive amyloid scan confirms the presence of AD pathology but can occur in cognitively normal older individuals. PET scans provide information about the underlying biology, which is integrated with the patient’s medical history, clinical symptoms, and structural imaging (MRI/CT). Structural imaging is used to rule out causes like tumors or stroke, and the combined data allows clinicians to formulate an accurate diagnosis.