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At Long Last, New Hope for Alzheimer’s Disease?

At Long Last, New Hope for Alzheimer’s Disease?

A nurse giving a patient new hope for Alzheimer's in a nursing home

At first glance, there seems to be no good news and little reason for hope when it comes to Alzheimer’s disease. Currently 5.7 million Americans are afflicted with Alzheimer’s at an annual cost to the nation of $227 billion.

Alzheimer’s disease is the sixth leading cause of death in the United States overall, and the fifth leading cause for those age 65 and older. This translates to one in three seniors dying of the condition.

In the absence of more effective prevention and treatment strategies, these numbers are projected to more than double to 14 million affected individuals – and more than quadruple to an annual cost of $1.1 trillion – by 2050.

Early Alzheimer’s Research Hampered by a Difficult Start

First, more bad news.

Forty years of financial investment and intensive research into treatments for Alzheimer’s and other neurodegenerative diseases has been one of modern medicine’s greatest disappointments, according to Zaven Khachaturian, editor-in-chief of “Alzheimer’s & Dementia” and former director of the Office of Alzheimer Research at the National Institutes of Health, writing in MedPageToday essays published in September and December 2018.

In fact, the failure rate for these drugs is a nearly-incomprehensible 99.6 percent, compared to cancer drugs which have a success rate of 20 percent. With odds like these, it’s no wonder some pharmaceutical companies have shuttered their Alzheimer’s disease units, raising concerns that others will follow suit.

The formal campaign against Alzheimer’s was launched by NIH’s National Institute of Aging in 1978. As Khachaturian describes, early efforts were hampered by the widespread conviction that Alzheimer’s was an unavoidable and incurable consequence of aging. Research into Alzheimer’s was initially viewed with as futile. These misconceptions have taken the scientific community about 25 years to overcome.

First-generation treatments, designed to slow the progression of Alzheimer’s cognitive-decline symptoms, became available as early as the mid-1990s. However, such drugs have been far from adequate due to the short-lived nature of their clinical effectiveness, roughly six to 24 months, due to the deterioration of neurons targeted by the drugs for improved intercellular communication.

Technological Advancements Yielded Improved, Ultimately Still Inadequate Interventions

In 2004, identification of Alzheimer’s hallmark brain lesions and other biomarkers through cutting-edge neuroimaging technology became possible, representing a significant breakthrough.

So-called “second generation” drugs have been intended to slow the progression of the disease process itself by preventing neuronal degeneration. This effort has apparently made frustratingly little progress over the past 25 years, leading a growing body of researchers to seek alternative approaches as clinical trials continue to go nowhere.

Nothing less than a complete revisioning of prevailing theories of Alzheimer’s disease as a basis for “radically new approaches” to drug development is required, according to Khachaturian, who admits that this kind of paradigm disruption is no small task for the scientific community.

Reasons for Optimism: An Increasingly Clear Understanding of Alzheimer’s Disease

Now for some much-needed good news.

Emerging insights into the nature of Alzheimer’s disease, Khachaturian insists, offer hope and direction for the development of more successful research strategies.

Heterogeneity 

  • Alzheimer’s disease manifests in a markedly-individual manner, with features and symptoms, risk factors and onset patterns varying widely among those affected. This suggests a need for the development of more individualized evaluation, treatment and case management approaches.

Multiple Complexities 

  • There appears to be multiple triggers for Alzheimer’s disease, not one single etiology. While this complexity poses a formidable research challenge, it also allows for more accurately-targeted investigations.
  • The onset of neuronal degeneration may occur decades earlier than expected, involving a rather prolonged preclinical or asymptomatic stage and indicating the need for the development of more sensitive screening tools for identification of asymptomatic yet at-risk individuals.

Better Identification of Risk Factors 

  • New information about genetic risk factors and the risks associated with comorbid chronic conditions open avenues for preventive strategies.
  • There’s mounting evidence that cardiovascular disease, including as early as mid-life, correlates with increased risk of dementia from all causes, not just Alzheimer’s.
  • Studies have shown that diabetes, hypertension, smoking and obesity (along with obesity’s metabolic and vascular comorbid factors) correlate with a higher risk of Alzheimer’s.
  • Preliminary evidence suggests that aggressive lowering of blood pressure lessens mild cognitive symptoms.

Lifestyle and Management 

  • Initial research into the effectiveness of lifestyle interventions and improved disease management appear promising.
  • Studies correlate a healthier diet with lower rates of cognitive decline or risk for Alzheimer’s disease and even improvements in overall cognitive performance.
  • Increased physical activity is associated with better cognition, lower cerebrospinal fluid markers, and delayed onset of cognitive symptoms in those with a rare form of Alzheimer’s

New Research Targets

  • Other new targets for research and therapeutic intervention include neuroinflammation, metabolic or mitochondrial dysfunction, and brain microvessel disease.

A Light at the End of a Long, Dark Alzheimer’s Tunnel?

Khachaturian manages to flip forty years of failed Alzheimer’s research on its head, finding the ensuing “loosening of dogmatic thinking” on the subject a potent silver lining that portends a better future.

While he may be a lone voice in a vast Alzheimer’s healthcare policy wilderness, for the sake of Alzheimer’s sufferers and their loved ones everywhere, we can only hope that he’s onto something.