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Brain perfusion SPECT in the diagnosis of Alzheimers disease

The Alzheimer's Association1 indicates 5.8 million Americans live with this cognitive disorder. The organisation calls it a national crisis, with the number of cases in this country expected to rise to 14 million by 2050. Early diagnosis of Alzheimer's disease (AD) can be helpful in delaying symptoms and preserving quality of life. Brain perfusion SPECT plays a vital role in supporting conventional diagnostic methods.

The challenge of diagnosing Alzheimer's disease

Dementia is a broad term encompassing disorders that cause a decline in mental capability to the extent of interfering with day-to-day life. AD is the most common form of dementia, yet this progressive neurodegenerative condition can be elusive. There is no definitive test to determine the presence of AD. Disease diagnosis often relies on an astute primary care provider, corroboration of memory loss, and other cognitive issues through interviews with the patient and family members and ruling out other possible causes such as medications and age-related depression.

AD is not solely an ailment of the elderly. While it is most prevalent in those over the age of 65, the youngest adult to incur the early-onset form of the disease was just 27 years old, and a closely related condition has been detected in very young children.1

Nerve cells in the brain communicate with one another through the release of chemicals, including acetylcholine, important to memory. Cholinesterase breaks down acetylcholine in the brain. Controlling this enzyme with drugs in a class called cholinesterase inhibitors shows great promise in improving:

  • Memory
  • Clear thinking
  • Daily functioning
  • Psychological and behavioral symptoms of AD

Dementia Australia2 reports that clinical trials support some value from cholinesterase inhibitors drugs for mild to moderately severe AD cases. There appears to be no difference in effectiveness based on age, gender, or ethnicity of the patient. However, this and other drug and non-drug therapies have been shown to provide greater benefit in patients who start treatment early in the course of the disease.

Adding to the challenge of diagnosing AD is that many other conditions such as psychiatric disorders, Parkinson's disease, and vascular dementia can mimic symptoms. Opportunities for the usefulness of drug therapy can be missed or reduced from delays caused by misdiagnosis. Inappropriate treatment is costly and may have an adverse impact on the patient. From a broader perspective, correct identification of the disease and tracking its progress aids researchers in exploring the effectiveness of future treatments and moving closer to a potential cure.

Brain Perfusion SPECT imaging can help physicians make a confident determination of AD sooner, for the most constructive treatment plan.

Brain perfusion SPECT is advantageous in early and accurate diagnosis of AD 

Alzheimer's disease is characterized by beta amyloid (Aβ) deposits and neurofibrillary tangles (NFTs) of abnormal hyper phosphorylated tau protein forming interneuronal plaques. These accumulations alter the formal function of neurons. They also damage blood vessels, disrupting the delivery of oxygen and glucose to the brain.3

An August 2018 report in Annals of Nuclear Medicine cites "Functional and molecular nuclear medicine imaging with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques provide valuable information about the underlying pathological processes, many years before the appearance of clinical symptoms."4

SPECT uses radioactive substances and a gamma camera to generate 3D images of internal organs. Cerebral perfusion pressure or CPP is the difference between mean arterial pressure and intracranial pressure, a measure of blood flow to the brain. A distinction of SPECT is that it highlights blood flow, essential for evaluation of brain and neurological conditions. PET is another functional nuclear imaging modality for the evaluation of regional cerebral perfusion.

Which technique makes more sense? The answer depends on more than clinical analysis alone. There are considerations that reach to the geographic and organisational levels. 

Multi-dimensional approach 

"Best interest of the patient" does not necessarily mean PET v. SPECT. In fact, these methodologies may be used solely, or in tandem, along with other forms of imaging.

A primary advantage of SPECT is its availability. The method is well established and has been widely used since the 1990s. More facilities are equipped with SPECT, due to a substantially lower initial price tag. SPECT radiotracers are less expensive than PET materials, controlling overall usage cost. The half-life of radiotracers used in SPECT is several hours, enabling greater flexibility in tracer uptake and scan times. PET radiotracers may have a shorter half-life5.

A decade ago, there were concerns with SPECT image quality – low resolution prone to artifacts (which could be mistakenly identified as perfusion defects), and attenuation – as well as quantifiable blood flow analysis. However, advances such as improved, multi-detector cameras, computer-aided image enhancements, hybrid SPECT/CT systems, novel reconstruction algorithms, and computer-aided image comparisons versus recognized normal blood flow characteristics have largely overcome those issues.

Emerging technology eliminates the need for structural images by using the data from medial and lateral brain surfaces with 3D stereotactic surface projection (3D-SSP). Data used frequently in the cross-sectional studies of dementia can then be used for intersubject comparisons with either t or z statistics. Combined with quantitative z-scores (measuring brain perfusion), the technology improves the workflow and enhances the serial imaging of patients. These qualities help monitor disease progression and may predict those who will eventually progress to AD6. 

This current generation of SPECT technology, however, does not negate the value of other imaging in the diagnosis of AD. Rather, they can be complementary.

Hiroshi Matsuda, MD, Ph.D., Director of the Integrative Brain Imaging Center, at the National Center for Neurology and Psychiatry in Kodaira, Tokyo, Japan, cites the benefits of a multi-modality approach. "To make a confident and early diagnosis of Alzheimer's or dementia, we must perform various tests and judge comprehensively." Dr. Matsuda goes on to say, "CT is the first imaging exam to eliminate the absence of physical factors, such as a brain tumor or cerebral infarction, that could account for cerebrovascular dementia6."

While an MRI (magnetic resonance imaging)-based regional voxel analysis can help to identify atrophy of the hippocampus, Dr. Matsuda emphasizes the benefit of adding a SPECT study. "Brain perfusion SPECT can clearly show clinical findings in patients who are in their 40s and 50s. However, in patients who are in their 70s, it may be difficult to differentiate mild dementia from AD. Therefore, a final diagnosis should be based on information from a combination of MRI and SPECT imaging test results. When used together, MRI and SPECT can provide a differential diagnosis in 70-80% of patient cases6."

Supplementing this information with amyloid PET imaging, where available, bolsters diagnosis further by reducing false positives.

Medical advances are helping to increase life expectancy, but AD is not a normal part of the aging process. Adding brain perfusion SPECT to diagnostic protocols can lead to treatment that has a positive impact on the lives of patients and their caregivers.

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References
  1. Alzheimer's and Dementia Facts and Figures. Alzheimer's Association.https://www.alz.org/alzheimers-dementia/facts-figures July 22, 2019
  2. Amyloid Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer’s disease Neurons. Journal of Alzheimer’s Disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793225/ September 11, 2019
  3. Drug treatments for Alzheimer's disease cholinesterase inhibitors. Dementia Australia.https://www.dementia.org.au/files/helpsheets/Helpsheet-DementiaQandA01-CholinesteraseInhibitors_english.pdf July 22, 2019
  4. SPECT and PET imaging in Alzheimer's disease. Annals of Nuclear Medicine.https://link.springer.com/article/10.1007%2Fs12149-018-1292-6 July 22, 2019.
  5. PET vs. SPECT - Will PET Dominate Over the Next Decade? Diagnostic and Interventional Cardiology.https://www.dicardiology.com/article/pet-vs-spect-will-pet-dominate-over-next-decade July 22, 2019
  6. Using Brain Perfusion SPECT with Q.Brain for Identifying Progression to Alzheimer's Disease. Clarity Magazine.https://www.gehealthcare.com//-/jssmedia/images/clarity/spect/using-brain-perfusion-spect-with-qbrain/4_6_nm_qbrain_cv_v9.pdf?la=en&hash=BF70C96A4FD65E7A7EB20D541BA6E227676B2D52 July 22, 2019.