Neurodegeneration — 12

People deemed at high risk must undergo further assessment and close surveillance. This includes a conventional brain MRI, or a resting-state functional MRI that can further differentiate risk and predict the disease up to nine years in advance. PET imaging, as used in the clinical trials, quantifies the levels of amyloid and Tau. Imaging can be done on a serial basis over time to determine whether there is progression and its rate. Add to this serial retina, brain organ clock, inflammatory marker assessments. Brain age, determined by AI of combined MRI and PET imaging, can be compared with chronological age and may prove useful as a means of tracking progression.

Multimodal AI of all these layers of data, indexed by time, can be used to establish the tempo of an individual’s condition, just as it has been used to accurately diagnose the many different types of dementia. It has also been used to predict the time frame of progression in people with mild cognitive impairment and evidence of β-amyloid accumulation. This could lead to aggressive interventions for lifestyle+ factors, use of anti-inflammatory drugs that are currently in clinical trials (such as GLP-1, or p75 drugs) or are demonstrating considerable potential, and, if need be, anti-amyloid treatment. This comprehensive approach is not yet validated but is worthy of rigorous assessment now.

Accurate definition of high risk would be critical for vaccines to protect against Alzheimer’s disease. There are multiple ongoing trials, such as AC Immune in Switzerland with two Alzheimer’s vaccines, one against β-amyloid and the other against Tau, or Vaxxinity in Florida, launching a clinical trial in three thousand participants with its amyloid directed vaccine. Six clinical trials are in progress in China, with vaccines directed to β-amyloid or Tau.

Meanwhile, as we await vaccines directed against Alzheimer’s disease, more evidence of an association of the recombinant shingles vaccine (Shingrix) with reduction of dementia, including Alzheimer’s, has emerged, which also raises the potential role of herpes zoster virus. Generally recommended for all people aged fifty years and older, this would be another specific consideration for high-risk individuals. Along with other reports, the potential tie-in of infections and Alzheimer’s is getting increasing attention. The possibility that Alzheimer’s may be caused by latent viruses, such as herpes or cytomegalovirus, has led to clinical trials with antiviral drugs.

PARKINSON’S DISEASE

Second to Alzheimer’s disease on the list of neurodegenerative disorders, Parkinson’s is on a steep rise of prevalence expected to affect as many as seventeen million people by 2040. More than two centuries since James Parkinson’s classic An Essay on Shaking Palsy, its pathogenesis remains unclear, and there are no validated disease-modifying treatments that stop or delay its progression. Age is the primary risk factor for both Parkinson’s and Alzheimer’s diseases. As is the case with Alzheimer’s, it takes decades for the underlying disease process to develop, begging for us to get a head start to interrupt it from occurring.