Every year on September 21st, the medical world focuses on raising awareness of Alzheimer’s disease (AD). Named after physician Alois Alzheimer, MD, AD is a neurodegenerative disorder that affects memory, cognitive function, and ultimately the ability to complete daily tasks. AD is currently the sixth leading cause of death in the US, but recent estimates suggest that the condition may be the third leading cause of death for older people, just behind heart disease and cancer.
In 1994, Alzheimer’s Disease International, an organization dedicated to supporting people living with the disease and accelerating related policies, instituted World Alzheimer’s Day in Edinburgh, Scotland, during their annual 10th anniversary conference . A decade and a half later, in 2009, that date marked the publication of the first World Alzheimer’s Report, which has been published every year since. This year’s report is again commissioned by McGill University to provide perspectives on post-diagnosis models of care through expert papers, case studies, perspectives from people living with the disease, and examples of best practice in post-diagnostic care.
To learn more about the meaning of World Alzheimer’s Day, NeurologyLive® sat down with Thomas M. Wisniewski, MD, director of the Alzheimer’s Disease Research Center at NYU Langone. As part of a new iteration of NeuroVoices, Wisniewski provided commentary on key aspects of AD care, the importance of caregiver burden and the current understanding of the pathology of the disease. He also emphasized advances in clinical research and the need to diversify drug development.
NeurologyLive®: Why is it important to recognize World Alzheimer’s Day? Are there aspects of Alzheimer’s disease that are not known to the general public?
Thomas Wisniewski, MD: Alzheimer’s disease and related dementias represent the growing public health crisis not only in the United States but worldwide. As the population ages here in the United States, but also around the world, the number of people living with Alzheimer’s disease and related dementias is expected to increase dramatically. This will have major societal and health implications. People with Alzheimer’s disease and related dementia require a lot of care and are extremely distressing for family members and their caregivers. It is also extremely expensive for the healthcare systems involved. There is great expectation that the numbers will increase almost exponentially in the coming decades.
In the US we currently have about 6.5 million affected Americans. This is associated with an estimated cost of around 325 billion US dollars this year. But by 2050, the number of affected patients in the US is expected to be around 13 million, at an estimated cost of nearly $1 trillion. Those are huge numbers, and it’s not just an issue for the western world. This also applies to developing countries and underdeveloped countries. It’s a world crisis. There have been many developments in Alzheimer’s disease, but until now we have not had a disease-modifying therapeutic approach. There are only therapies that are symptomatic. There is a possibility that we may have some disease-modifying approaches on the horizon, although that really remains to be seen. But it’s an exciting time for research and the promise of potentially better therapeutic interventions.
How has our understanding of Alzheimer’s disease improved over the years?
The pathology of Alzheimer’s disease is reasonably well understood. It is related to the accumulation of amyloid-ß in amyloid plaques, neuritic plaques, as well as the accumulation of abnormally phosphorylated tau protein that forms neurofibrillary tangles. Amyloid ß protein also accumulates in cerebral blood vessels in a so-called cerebral amyloid angiopathy as well as vascular amyloid, which is also an important component of the pathology of Alzheimer’s disease. For both amyloid-β protein and abnormally phosphorylated tau protein, the soluble oligomeric species of amyloid-β and tau are believed to be the most toxic and most responsible for neuronal dysfunction and death. This is an important therapeutic goal for many of the emerging approaches.
Despite these frequent lesions, it has become clear that the pathogenesis of Alzheimer’s disease is heterogeneous. In the very rare early-onset forms of Alzheimer’s disease associated with mutations and genes PSEN1 and PSEN2 in the amyloid precursor protein – accounting for less than 1% of the total [population]– There is the overproduction of amyloid-ß that fuels the process due to the mutations in these particular genes. But in the much more common late-onset forms of Alzheimer’s disease, over 30 different genes have been identified in various genome-wide association studies. They are located on different pathways in cholesterol metabolism, immune function, endosomal lysosomal function, synaptic function, etc. The drivers of the disease are multiple; therefore, the therapeutic approaches that may be considered must also be diverse.
Previously, most pre-clinical and clinical studies were very amyloid-centric. Almost all target amyloid-ß on the plaque side, but in recent years that has not been the case. Various objectives are examined. These approaches are not mutually exclusive, they can be refined to a certain extent to specific subgroups of Alzheimer’s disease with their specific underlying pathogenesis. Given the type of Alzheimer’s disease and the stage that a particular patient is in, and hopefully in the future when we may have a whole range of different approaches looking at different pathogenic pathways, we can be much more specific in our approach tackle Alzheimer’s disease. While the basic lesions and what happens within those lesions are well understood, we still understand what ultimately drives the emergence of this pathology. It is very complex, and the approaches evaluated help to address this type of complexity.
Which symptoms continue to cause the most problems?
It is certainly important for clinicians to recognize that Alzheimer’s disease affects the entire dyad or family unit. As you optimize your treatment of the patient, you also need to address the concerns of caregivers, the stress that the condition is putting on them, and ensure that one can optimize the support structures that allow the caregiver to optimize care patient and relieve their stress. We have approximately 6.5 million Americans with Alzheimer’s disease and related dementias, but it is estimated that approximately 11 million Americans provide unpaid care to affected individuals. That is estimated to be around 16 billion hours of care dedicated to these people and if compensated would cost $272 billion. Physicians need to mitigate the level of care required and the stress it entails. Addressing these nurses’ concerns is ultimately something that aids the patient’s care, delays the need for institutionalization, and contributes to their overall well-being. It’s just the realization that one cannot just focus on diagnosing the patient, but that looking at the entire family and caregiver structure is an important consideration.
Transcript edited for clarity. Click here for more NeuroVoices.