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Alzheimer’s Disease—Is an Endgame in Sight?

January 06, 2015

By Marc Agronin, MD
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The opinions expressed by Psychiatry & Behavioral Health Learning Network bloggers and those providing comments are theirs alone and are not meant to reflect the opinions of the publication.

Here is an unfortunate paradox: Alzheimer’s disease is, according to a recent article in the New England Journal of Medicine by Hurd and colleagues, the most expensive illness in the United States. Both the number of sufferers and the costs are increasing exponentially.

However, money spent by the National Institutes of Health on Alzheimer’s disease research has actually decreased in recent years, and total research for Alzheimer’s disease is less than one-fifth of that for cancer and heart disease, respectively. The widely touted National Alzheimer’s Plan, while welcomed and well-intentioned, is less than the proverbial drop-in-a-bucket when set against the soaring economic needs of patients and caregivers alike. And despite several billion dollars in pharmaceutical research over the past ten years, no new treatments have demonstrated sufficient efficacy to gain FDA approval. Is there an endgame in sight?

The current theory for Alzheimer’s disease focuses on the build-up of extracellular beta-amyloid protein in the brain as the “trigger”, and the subsequent destabilization of intracellular tau protein as the “bullet” that causes neurodegeneration for years (if not decades), eventually resulting in clinical symptoms. It has become alarmingly clear that by the time an individual presents with symptoms of Alzheimer’s disease, any treatment to slow or stop the underlying pathology is too little, too late.

The FDA will thus accept the slowing of disease progression as a reasonable outcome measure rather than only requiring symptomatic improvement. This change is key to the crop of immunotherapies in active research, particularly the anti-amyloid antibody solanezumab, which has shown over 30% disease slowing in preliminary data from clinical trials.

The main scientific advance for Alzheimer’s disease has been in early detection of beta-amyloid plaque build-up via CSF analysis and / or PET scans using amyloid radio-ligands such as florbetapir, flutemetamol, and others. Early detection is not a guarantee of diagnosis (as over 20% of individuals positive for beta-amyloid are cognitively normal) but with time may emerge as a critical harbinger of disease.

The identification of very early stage disease (particularly the preclinical stage according to the new National Institute of Aging – Alzheimer’s Association staging) may be the key to slowing or even stopping the wildfire of Alzheimer’s disease when it is merely a puff of smoke. The final lesson for all clinicians should be aggressive memory screening and referral to clinical trials— many of which are looking for early stage disease and offer free PET scans coupled with the possibility of actually doing something about positive results. These trials do not appear to represent an endgame in this disease, but they are progress.


Hurd, M.D., Martorelli, P., Delavande, A. (2013). Monetary costs of dementia in the United States. N Eng J Med. 368(14), 1326-1334.

Eli Lilly (2012). Eli Lilly and Company Announces Top-Line Results on Solanezumab Phase 3 Clinical Trials in Patients with Alzheimer's Disease (Press release, August 24, 2012). Accessed June 21, 2013 at:

Tayeb, H.O., Murray, E.D., Price, B.H., Tarazi, F.I. (2013). Bapineuzumab and solanezumab for Alzheimer's disease: is the 'amyloid cascade hypothesis' still alive? Expert Opin Biol Ther, 13(7):1075-84.

Marc E. Agronin, MD is Medical Director for Mental Health and Clinical Research,Miami Jewish Health Systems, Miami,   FL. He also is Affiliate Associate Professor of Psychiatry and Neurology, University of Miami Miller School of Medicine, Miami, FL.

The views expressed on this blog are solely those of the blog post author and do not necessarily reflect the views of Psych Congress Network or other Psych Congress Network authors.

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