Month: February 2024

Currently, there is no single, simple diagnostic test for Alzheimer’s. Developing a straightforward, non-invasive, and inexpensive early diagnostic test could aid in early diagnosis and the targeting of new Alzheimer’s medications to those in the early stages of the disease. Recently, a team of researchers has discovered a blood test that detects a specific type of tau protein. This test can potentially help identify changes in amyloid and tau in the brain.

Researchers have discovered a novel, potentially useful diagnostic tool for early Alzheimer’s diagnosis that provides a non-invasive, commercially feasible method for early illness detection in clinical settings.

According to a new study published in JAMA Neurology, a blood test used to screen for Alzheimer’s shows promise in identifying changes in brain levels of tau and amyloid beta proteins years before symptoms develop [1].

Even though Alzheimer’s affects over 55 million people globally, there is no reliable and straightforward method for diagnosing the disorder [2]. According to the Centers for Disease Control and Prevention (CDC), this has resulted in a situation where less than half of dementia patients in the US have a medical diagnosis [3].

When diagnosing dementia, doctors typically take a patient’s medical history, rule out other dementia kinds (such as vascular dementia), and perform testing on the cerebrospinal fluid or scans. All of these are costly, time-consuming, and even invasive.

Identifying the disease in its early stages is challenging when testing is inaccurate. As a result, the few treatment options available for Alzheimer’s cannot be initiated early (when they may be most beneficial), and it is also difficult to design trials to establish whether certain medications might be effective if taken early in the disease.

Can a blood test for Alzheimer’s aid in an early diagnosis?

Scientists have been searching for a simple blood or saliva test to identify if an individual has the typical build-up of tau and amyloid beta in their brain. The blood-brain barrier restricts the quantity of substances present in the brain from entering the bloodstream, which is one of the obstacles in creating a blood test. Furthermore, the proteins tau and amyloid are sticky by nature.

Researchers have conducted much research to identify the type of tau in the blood that most likely indicates elevated levels of amyloid and tau in the brain and not anywhere else in the body. Previous studies have examined the ratio of specific types of amyloid beta to other forms, and p-tau217 has surfaced as a tau variant that indicates the formation of amyloid and tau accumulation in the brain [4].

A company, AD-Detect, developed and released a blood test in 2023 to detect amyloid beta proteins. In addition, they designed the ALZpath pTau217 assay, which is exclusive to researchers and enables them to identify this particular kind of tau through a blood test [5].
An international group of scientists from Scandinavia, Europe, and the US were given access to this test free of charge to see how this test compared to employing cerebrospinal fluid to detect Alzheimer’s biomarkers.

Neurological detection of tau and amyloid beta proteins via blood test

In the recent research, researchers examined information from three sources: two biobanks established to study aging and dementia and one cohort of people at risk for Alzheimer’s [1]. The study involved 786 participants—504 female and 282 male—with a mean age of 66. The subjects underwent brain scans and spinal taps, and the researchers collected their blood.

During the data collection process, some subjects displayed indications of cognitive deterioration while others did not. With p-tau217 immunoassay, the researchers were able to identify aberrant beta amyloid and tau in a participant’s blood sample with comparable accuracy and findings compared to the participant’s spinal tap or brain scan.

Data analysis revealed that while the assay could detect people with aberrant levels of tau and amyloid beta, it did not examine a potential correlation between these abnormalities and the occurrence of Alzheimer’s. Researchers evaluated the assay combined with imaging data.

The assay was comparable to cerebrospinal fluid assays in its capacity to identify aberrant levels of tau and amyloid beta, and it offered a more precise diagnosis of hippocampal shrinkage. This was true for each of the three groups.

According to the researchers, 80% of test subjects had aberrant tau and amyloid beta levels that the assay could identify; the other 20% would require cerebrospinal fluid testing or further imaging. They stated that it might help identify patients for early intervention with novel pharmaceutical treatments intended to lower amyloid formation and was more accurate than the diagnostic techniques available today.

The assay creators vetted the publication before its submission to the journal.

The possible limitations

However, while the blood test in this study turned out to be highly accurate in identifying whether someone has significant Alzheimer’s traits in their brain, not everyone who has those characteristics would get the disease.

Additionally, as the p-tau test is only specific for Alzheimer’s, it cannot rule out other probable causes of symptoms such as vascular dementia or Lewy body dementia in patients who test negative but exhibit evidence of cognitive impairment.

In conclusion, a blood test for Alzheimer’s, such as the one illustrated in the new study, can be used to help diagnose both an individual undergoing early memory loss and a patient before they exhibit signs or symptoms of the disease because changes in the brain can occur up to 20 years before overt symptoms appear.

References

1. Ashton, N.J., Brum, W.S., Di Molfetta, G., Benedet, A.L., Arslan, B., Jonaitis, E., Langhough, R.E., Cody, K., Wilson, R., Carlsson, C.M. and Vanmechelen, E., 2024. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA neurology.
2. Dementia. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/dementia. Accessed: 12th February, 2024.
3. Advancing Early Detection. Alzheimer’s Disease and Healthy Aging. Centers of Disease Control and Prevention. https://www.cdc.gov/aging/healthybrain/issue-maps/early-detection.html. Accessed: 12th February, 2024.
4. Telser, J., Risch, L., Saely, C.H., Grossmann, K. and Werner, P., 2022. P-tau217 in Alzheimer’s disease. Clinica Chimica Acta, 531, pp.100-111.
5. pTau217: A Transformative Biomarker for Alzheimer’s Disease. ALZpath. https://alzpath.bio/researchers/. Accessed: 12th February, 2024.
6. Blood test may detect early signs of Alzheimer’s in the brain, study suggests. Medical News Today. https://www.medicalnewstoday.com/articles/alzheimers-blood-test-detect-early-signs-protein-buildup-in-brain. Published Online: 25th January, 2024. Accessed: 12th February, 2024.
7. New blood test that screens for Alzheimer’s may be a step closer to reality, study suggests. CNN Health. https://edition.cnn.com/2024/01/22/health/alzheimers-blood-test-screening-study/. Published Online: 22nd January, 2024. Accessed: 12th February, 2024.

Dementia is a neurological condition that impairs cognitive functions such as memory, language, and the ability to recognize and deal with emotions. Dementia with Lewy bodies (DLB) is among the most common kinds of dementia.

Understanding more about the potential involvement of gender and sex in DLB has gained attention recently. Researchers at Karolinska Institutet have addressed this issue of sex differences in DLB in two recent papers.

Sex differences in dementia with lewy bodies (DLB)

Dementia care is shifting away from treating all patients in the same manner. Instead, how dementia is identified and treated depends on the distinctive characteristics of each patient, such as their age, sex, lifestyle, or past medical history. This customized approach is especially crucial in diseases that manifest differently in various patients, such as dementia with Lewy bodies (DLB).

Given the high proportion of men with DLB compared to women, it has long been assumed that sex plays a significant role in the condition. However, the reasons underlying this discovery remain unclear.

A recent study has helped to highlight that men and women with DLB have distinct symptoms. Women with DLB typically have more visual hallucinations, whereas males with DLB are more likely to have movement issues and dream sleep disturbances.

The recent study

Dr. Javier Oltra and associates in the Ferreira lab released a study in December 2023 that has contributed to our growing knowledge of the disease’s impact on the brains of male and female DLB patients. Drs. Oltra, Habich, Ferreira, and associates facilitated an extensive global collaboration between scientists at the Karolinska Institute, the University of Barcelona, the European DLB consortium, and the Mayo Clinic in Rochester, U.S.

The researchers jointly explored how a patient’s sex would impact DLB-related brain tissue loss. The journal Alzheimer’s and Dementia published the investigation’s findings [1]. The researchers examined the world’s largest DLB imaging dataset, which included 442 patients from 14 centers throughout Europe and the Mayo Clinic in the United States.

The researchers defined brain matter loss using two different methodologies. In the first approach, a specialized medical specialist visually examined images of the brain and determined whether brain matter loss happens in substantial parts of the brain. This method is straightforward but effective because it is used in clinical practice today, making it easier to translate research findings into clinical practice. The second approach evaluated the loss of brain tissue in smaller brain regions using a sophisticated, automated process.

The study found that men with DLB lose more brain matter than women with DLB in several brain regions, especially in the frontal lobe. Interestingly, these sex differences were evident in younger patients and reduced at older age, with differences between men and women with DLB diminishing at the age of 75. Additionally, the researchers demonstrated that cognitive issues and the occurrence of visual hallucinations were linked to men’s regional loss of brain matter.

Ongoing Research

Expanding upon these gender disparities in DLB brain loss, the group carried out a second study under the direction of Dr. Annegret Habich, but from a network perspective this time [2]
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By employing the network technique, rather than concentrating on a single brain region at a time, we can examine intricate patterns of brain matter loss that appear across numerous brain regions. It is crucial because the illness that causes DLB, known as the “Lewy body disease,” is thought to cause brain matter loss and spread across the brain via these brain networks rather than staying in one specific area of the brain.

According to their research, sex differences in brain networks mostly occurred between men and women in good health; however, sex differences were less pronounced in DLB patients.

Consistent with the earlier research, these results underscore the significance of sex in DLB and may account for the distinct ways in which the illness spreads throughout the brains of men and women until the point at which the sex differences vanish during the dementia phase of the condition.

The combined results of these two investigations point to an earlier onset of brain matter loss in males with DLB. In contrast, women with DLB experience a more aggressive course of brain matter loss that begins later.

As a result, while women and men with DLB eventually attain equal degrees of disease severity, their disease processes can differ dramatically.

Raising awareness about this issue will assist physicians in detecting the condition earlier and more accurately in women and men with DLB, which is the initial step toward providing patients with sufficient dementia care and treatment options.

References

1. Oltra, J., Habich, A., Schwarz, C.G., Nedelska, Z., Przybelski, S.A., Inguanzo, A., Diaz‐Galvan, P., Lowe, V.J., Oppedal, K., Gonzalez, M.C. and Philippi, N., 2023. Sex differences in brain atrophy in dementia with Lewy bodies. Alzheimer’s & Dementia.
2. Habich, A., Oltra, J., Schwarz, C.G., Przybelski, S.A., Oppedal, K., Inguanzo, A., Blanc, F., Lemstra, A.W., Hort, J., Westman, E. and Lowe, V.J., 2023. Sex differences in grey matter networks in dementia with Lewy bodies.
3. A type of dementia that hits the brain of men and women differently. News from Karolinska Institutet. https://news.ki.se/a-type-of-dementia-that-hits-the-brain-of-men-and-women-differently. Published Online: 22nd January, 2024. Accessed: 9th February, 2024.
4. A type of dementia that hits the brains of men and women differently. Medical Xpress. https://medicalxpress.com/news/2024-01-dementia-brains-men-women-differently.html. Published Online: 23rd January, 2024. Accessed: 9th February, 2024.

Alzheimer’s impacts the brain but may also affect the eyes. A recent study found that almost 94% of participants with an unusual vision problem also exhibited Alzheimer’s pathology. Researchers emphasized the need for further clinical understanding of posterior cortical atrophy (PCA) to aid in the early detection of Alzheimer’s.

Alzheimer’s is well recognized to affect brain skills such as memory, spatial awareness, speaking, and writing, but what is not much known are the changes to the brain that may also affect the eyes [1].

Previous research indicates that alterations in the brain associated with Alzheimer’s may also transpire in the retina [2]. Additionally, researchers have observed abnormalities in the eyes with Alzheimer’s, such as loss of visual field, color vision, and contrast sensitivity needed for reading [3,4].

In a recent study published in The Lancet Neurology, scientists from the University of California, San Francisco, investigated the impact of a rare eye disorder called posterior cortical atrophy (PCA), often known as Benson’s syndrome, to see how Alzheimer’s affects the eyes [5]. According to this study, some people—women in particular—may have impairments in their visual perception even when their cognitive abilities appear normal.

The Recent Research Findings

Researchers looked at data from nearly 1,100 patients with posterior cortical atrophy (PCA), a disorder characterized by shrinkage of brain tissue in areas of the brain involved in processing and responding to visual information. In daily life, this can result in issues with reading comprehension or driving depth perception, particularly at night.

Autopsy results revealed that 94 percent of these patients displayed symptoms consistent with Alzheimer’s, indicating that it virtually always causes PCA.

According to the National Institutes of Health, PCA is typically diagnosed at age 59, which is five or six years earlier than the average diagnosis of Alzheimer’s. Women are more likely to get it than men; they make up 60% of cases [6].

The study discovered that although the majority of PCA patients may initially exhibit normal cognitive function, it might take up to four years for them to receive a diagnosis. By then, they frequently suffer from mild to moderate dementia, which includes impairments in speech, behavior, memory, and executive function.

However, according to principal study author Marianne Chapleau, PhD, a neuropsychologist and postdoctoral fellow in neurology at the University of California, San Francisco, many people may be unaware that they have PCA or that it can be an early Alzheimer’s sign.

Dr. Chapleau states that because people tend to link visual problems to aging vision rather than dementia, visual symptoms in PCA may manifest before more prominent and widespread cognitive deficits linked with Alzheimer’s disease. Consequently, they miss out on the chance for earlier intervention.

Visual Perception Issues

At the time of their PCA diagnosis, 61% of research participants experienced what is known as “constructional dyspraxia,” or the inability to duplicate basic designs or figures. Furthermore, about half of them struggled to identify the locations of things they observed and to perceive more than one object at a time.

According to Andrew Budson, MD, chief of cognitive behavioral neurology at VA Boston, a neurology professor at Boston University (who was not involved in the study), it makes sense that when someone exhibits these symptoms, they might not think of Alzheimer’s. They typically visit their optometrist first to have the prescription for their glasses corrected; if the optometrist is unable to assist, they may then visit an ophthalmologist. Only at that point, the ophthalmologist might refer the patient to a neurologist, realizing that the issue is probably in the brain rather than the eyes.

However, a PCA diagnosis may not even result from that initial neurology session. Individuals may still require an MRI that reveals brain shrinkage patterns that are consistent with PCA, as well as a visit with a dementia or memory disease specialist.

Advantages of an Early Diagnosis

Budson emphasized the importance of receiving a PCA diagnosis as soon as possible because there are strategies people can take to manage their symptoms. Since Alzheimer’s disease is often the cause of PCA, treatment with anti-amyloid medications, such as lecanemab (Leqembi), may reduce the symptoms.

While more research is needed, it may be feasible to diagnose PCA in its earliest stages and prevent it from worsening with these Alzheimer’s treatments.

Although there is no known cure for PCA, lifestyle modifications can still have a positive impact.

According to Dr. Chapleau, maintaining a healthy lifestyle, including cognitive activities, a balanced diet, and regular exercise, may improve overall brain health. After a diagnosis, therapies such as cognitive therapies, medication, and customized care plans can help manage symptoms and decrease the progression of dementia.

References

1. Hussain, A., Sheikh, Z. and Subramanian, M., 2023. The Eye as a Diagnostic Tool for Alzheimer’s Disease. Life, 13(3), p.726.
2. Koronyo, Y., Rentsendorj, A., Mirzaei, N., Regis, G.C., Sheyn, J., Shi, H., Barron, E., Cook-Wiens, G., Rodriguez, A.R., Medeiros, R. and Paulo, J.A., 2023. Retinal pathological features and proteome signatures of Alzheimer’s disease. Acta Neuropathologica, 145(4), pp.409-438.
3. Romaus-Sanjurjo, D., Regueiro, U., López-López, M., Vázquez-Vázquez, L., Ouro, A., Lema, I. and Sobrino, T., 2022. Alzheimer’s disease seen through the eye: ocular alterations and neurodegeneration. International Journal of Molecular Sciences, 23(5), p.2486.
4. Kim, H.J., Ryou, J.H., Choi, K.T., Kim, S.M., Kim, J.T. and Han, D.H., 2022. Deficits in color detection in patients with Alzheimer disease. Plos one, 17(1), p.e0262226.
5. Chapleau, M., La Joie, R., Yong, K., Agosta, F., Allen, I.E., Apostolova, L., Best, J., Boon, B.D., Crutch, S., Filippi, M. and Fumagalli, G.G., 2024. Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis. The Lancet Neurology, 23(2), pp.168-177.
6. What Are the Signs of Alzheimer’s Disease? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-symptoms-and-diagnosis/what-are-signs-alzheimers-disease. Accessed: 2nd February, 2024.
7. Pelc, C. Alzheimer’s may begin with unusual vision problems, study finds. Medical News Daily. https://www.medicalnewstoday.com/articles/rare-eye-condition-linked-to-alzheimers. Published Online: 25th January, 2024.
8. Rapaport, L. Visual Perception Problems May Be an Early Alzheimer’s Sign, Especially in Women. Everyday Health, https://www.everydayhealth.com/alzheimers-disease/visual-perception-problems-may-be-an-early-alzheimers-sign-especially-in-women/. Published Online: 24th January, 2024. Accessed: 2nd February, 2024.