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Alzheimers and Dementia

 

Dementia is a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Alzheimer’s is the most common cause of dementia, accounting for 60-80% of dementia cases. While memory loss and decaying cognitive function is recognized as a symptom of old age, Alzheimer’s is not a normal part of aging. The greatest known risk factor for Alzheimer’s is increasing age with the majority of those suffering from Alzheimer’s being 65 or older. However, Alzheimer’s is not exclusive to the elderly. Approximately 200,000 Americans under the age of 65 have early-onset Alzheimer’s.[1]

Alzheimer’s is a progressive disease, where dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late-stage Alzheimer’s, individuals lose the ability to converse and respond to their environment. Eventually the disease leads to the deterioration of the body and currently Alzheimer’s is the sixth leading cause of death in the United States. The average life expectancy for a person diagnosed with Alzheimer’s is 4-8 years.[2]As with many diseases and disorders, treatment for Alzheimer’s is more effective the earlier the disease is discovered. There is currently no test that allows for the detection of Alzheimer’s before the initial symptoms have presented themselves. There is evidence to suggest that the pathophysiological process that leads to Alzheimer’s begins years, if not decades before a clinical diagnosis is made.[3]Alzheimer’s can only be definitively diagnosed after death. As such, there is a dire need for a non-invasive diagnostic test that can clearly detect Alzheimer’s in its early stages.

 

There is evidence to suggest that certain biomarkers could enable early identification of characteristic pathologic alterations before neuronal damage develops. Alzheimer’s specific alterations in cerebrospinal fluid biomarkers that reflect the neuronal changes have emerged as reliable analytes associated with eventual pathologic confirmation.[4]A major drawback of this approach is the invasive lumbar puncture required to collect the cerebrospinal fluid, which would pose a high risk to elderly patients. A novel diagnostic approach exists that relies on the identification of patterns of volatile organic compounds (VOCs) in exhaled breath.
 

Several studies have been able to successfully differentiate between patients diagnosed with Alzheimer’s disease and healthy controls. In 2013, Tisch et al.published a ground-breaking study that took 15 diseased patients and compared breathprints with 12 healthy controls. The test was able to differentiate the subjects with 79-85% accuracy. The breath samples collected were also analyzed using GC-MS to determine potential biomarkers indicative of Alzheimer’s disease. The researchers tentatively identified 24 compounds that are present in >80% of test subjects and at elevated concentrations in the Alzheimer’s disease patient group.[5]Building off this initial study, Mazzatenta et al.published a study in 2015 that compared the breath between 15 diseased patients and 44 healthy controls. The researchers clearly demonstrated a difference in VOC concentrations and suggested that Alzheimer’s disease is characterized by a fingerprint of clustered VOCs rather than just a few compounds.[6]Later in 2015, Bach et al.identified 4 compounds that were capable of differentiating Alzheimer’s patients from healthy controls. However, this study faced issues with reproducibility in a follow up study with patients at a second hospital.[7]Further studies with larger sample sizes are required to validate breath analysis as a tool in the detection of Alzheimer’s disease, but the preliminary results look very promising.

References

[1]What is Alzheimer’s? https://alz.org/alzheimers-dementia/what-is-alzheimers(accessed Jun 5, 2019).

[2]How Is Alzheimer’s Disease Diagnosed? https://www.nia.nih.gov/health/how-alzheimers-disease-diagnosed(accessed Jun 5, 2019).

[3]Meyer, G. D.; Shapiro, F.; Vanderstichele, H.; Vanmechelen, E.; Engelborghs, S.; Deyn, P. P. D.; Coart, E.; Hansson, O.; Minthon, L.; Zetterberg, H.; et al. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol2010, 67(8), 949–956.

[4]Barba, I.; Fernandez‐Montesinos, R.; Garcia‐Dorado, D.; Pozo, D. Alzheimer’s Disease beyond the Genomic Era: Nuclear Magnetic Resonance (NMR) Spectroscopy-Based Metabolomics. Journal of Cellular and Molecular Medicine2008, 12(5a), 1477–1485.

[5]Tisch, U.; Schlesinger, I.; Ionescu, R.; Nassar, M.; Axelrod, N.; Robertman, D.; Tessler, Y.; Azar, F.; Marmur, A.; Aharon-Peretz, J.; et al. Detection of Alzheimer’s and Parkinson’s Disease from Exhaled Breath Using Nanomaterial-Based Sensors. Nanomedicine2012, 8(1), 43–56.

[6]Mazzatenta, A.; Pokorski, M.; Sartucci, F.; Domenici, L.; Di Giulio, C. Volatile OrganicCompounds (VOCs) Fingerprint of Alzheimer’s Disease. Respiratory Physiology & Neurobiology2015, 209, 81–84.

[7]Bach, J.-P.; Gold, M.; Mengel, D.; Hattesohl, A.; Lubbe, D.; Schmid, S.; Tackenberg, B.; Rieke, J.; Maddula, S.; Baumbach, J. I.; et al. Measuring Compounds in Exhaled Air to Detect Alzheimer’s Disease and Parkinson’s Disease. PLOS ONE2015, 10(7), e0132227.

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