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A complete solution for patients with Alzheimer’s disease may be on the horizon

New treatments and improved diagnostic and staging tools will allow for a complete solution for Alzheimer’s disease in the future, that was the key messages of a forward-thinking symposium at the 11th CTAD congress. New self-assessment tools may be provided to individuals concerned about their cognitive health, utilizing digital technology. Advances with blood biomarkers, ultrasensitive immunoassays, and new imaging techniques will provide early screening tools and may serve as biomarker outcomes for developing new therapies. Ultimately, management of this multi-factorial disease will require a combination of treatments with different mechanisms, that may be furnished from treatments currently in clinical development.

New treatments, improved methods for identifying individuals in the earliest stages of disease, and improved diagnostic and staging tools may allow development of a complete solution for patients with Alzheimer’s disease said Dr Rachelle Doody, Global Head of Neurodegeneration at Roche, Switzerland, introducing a symposium at the 11th CTAD congress. Progress towards a complete solution could start by providing self-assessment tools to individuals who are concerned about their cognitive health, developing more accurate clinical tools to stage disease, and providing a range of treatment options for patients at all stages of Alzheimer’s disease.

Self-detection of cognitive problems is indeed possible and has been demonstrated in multiple studies,1,2 said Dr Mary Sano, Alzheimer’s Disease Research Center, Icahn School of Medicine at Mt. Sinai, New York, USA. A recent meta-analysis suggests that the presence of subjective memory concerns doubles the likelihood that a person has or will develop dementia,3 she added.

Digital technologies, such as smartphones and wearables, offer the potential to do even better in capturing both subjective and objective measures of cognition. The use of smartphones among those aged over 50 is rising,4 and a proof-of-concept study (iVitality) has shown high compliance (60% over 6 months) with cognitive testing using a smartphone app among people at increased risk of dementia (family history, mean age 57 years).5

 Smartphone apps could enable early identification of cognitive problems in people at risk of Alzheimer’s disease

Advances in identifying plasma amyloid-b (Ab) biomarkers offer huge advantages for screening and diagnosis in terms of reduced cost and much greater availability to large populations,6-8 said Dr Christopher van Dyck of the Alzheimer’s Disease Research Unit, Yale University, USA. The Trial-Ready Cohort for Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) project will incorporate three different plasma biomarker assay platforms, which will enable multi-center comparative field testing of the assessment tools.

Advances with blood biomarkers, ultrasensitive immunoassays, and new imaging techniques will provide early screening tools and may serve as biomarker outcomes for developing new therapies

Ultrasensitive immunoassays for Ab oligomers in cerebrospinal fluid (CSF) offer the ability to demonstrate target engagement in clinical trials and may serve as biomarker outcomes for developing therapies.9 In addition, a ligand (binding to synaptic vesicle glycoprotein 2) for synaptic position emission tomography (PET) imaging,10 developed by the Yale Center, could offer the first in vivo measure of synaptic density as an outcome measure in clinical trials of disease-modifying therapies, particularly those targeting synapses.

There is little doubt that this complex disease will be treated with combination therapies in future, said Professor Dennis Selkoe of the Brigham and Women’s Hospital and Harvard Medical School, Boston, USA. Like other chronic, multifactorial diseases, Alzheimer’s disease may be treated with a combination of two or more disease-modifying agents that target the same or different pathogenic factors, he said.

Alzheimer’s is a complex disease that will be best treated with combination therapies

Professor Selkoe suggested a new approach to treating Alzheimer’s disease, beginning with risk assessment in mid-life to generate an Alzheimer’s disease risk score. This score would incorporate family history, results from a cognitive screen and neuropsychological testing, genetic testing, plasma biomarkers, imaging studies, and CSF testing. The treatment approach would be designed based on the Alzheimer’s disease risk category into which a person falls.

The best approach to treatment may be to start with one agent with proven benefits before adding a second agent. At least one of the agents should neutralize or clear diffusible Ab-oligomers said Professor Selkoe, since they increasingly appear to be pathogenic.11 The second drug could be an anti-tau agent or target Ab through a different mechanism.

Further reading: It’s in the blood – identification of plasma biomarkers brings hope for screening and early detection of Alzheimer’s disease.

References
  1. Schofield PW et al. Am J Psychiatry. 1997;154:609-15.
  2. Li C et al. J Alzheimers Dis. 2017;60:427-37.
  3. Mitchell AJ e tal. Acta Psychiatr Scand. 2014;130:439-51.
  4. Anderson GO. AARP Research, December 2017. Washington, DC https://doi.org/10.26419/res.00210.001
  5. Jongstra S et al. JMIR mhealth uHealth 2017;5:e68.
  6. Ovod V et al. Alzheimers Dement. 2017;13:841-9.
  7. Nakamura A e tal. Nature 2018;554:249-54.
  8. Hansson O et al. AAIC Chicago, IL, July 22-26; 2018: oral presentation.
  9. Yang T et al. Alzheimers Res Ther. 2015;7:14.
  10. Chen MK et al. JAMA Neurol. 2018: 75:1215-24.
  11. Jin M et al. Nat Commun. 2018;9:2676.
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