Are Disease Modifying Treatments Enough? Improving Quality of Life in Late-Stage Patients

Watt et al. [1] highlight the importance of considering the societal and patient-specific effects of dementia severity when disease modifying treatments are given to patients. The impact of halting disease progression in a late-stage dementia patient is that the patient could be left in an interminable state of disability if restorative therapies are unavailable. This situation raises the absolutely critical question of considering the context in which therapies operate. It also highlights the importance of therapies that improve the lives of late-stage patients.

Watt et al. suggest that there may be a point in Alzheimer’s disease (AD) progression that is not worth prolonging, but this view does not consider the possibility that therapies may improve patients’ experiences. There must thus be a dual focus of clinical research on both disease modifying therapies and treatments that enable even patients with advanced dementia to achieve lives they feel are worth living. This task has been operationalized as the study of therapies directed at improving patients’ general well-being, a concept typically referred to as quality of life (QOL). The field studying QOL in advanced dementia patients currently faces challenges in measurement. For noncommunicative patients highly reliable measures based on staff observations are available [2, 3]. There are many different dimensions of QOL that have been studied in dementia patients [4]. What constitutes a life worth living is fluid throughout the progression of dementia [5]. Early stage patients may prioritize independence as they lose the ability to work, while late-stage patients may value the community of other residents at a dinner table; both are expressions of QOL. Evaluations of what constitutes a life worth living and how to optimize QOL thus need to be responsive to dementia severity. When discussing disease modifying therapies with patients and next-of-kin, it is also important to discuss current and anticipated capabilities of QOL enhancing interventions. There have already been interventions in late-stage dementia patients that demonstrate statistically significant improvements in QOL [6]. With the advent of disease modifying treatments, improvements must not only aim to understand and tailor goals relevant to late-stage patients, but also aim for clinical significance to merit prolonging life from the patient’s perspective.

Improving functioning in damaged brains with restorative therapies will be more appealing with the knowledge that a degenerative process is now stopped with disease modifying treatments. Invasive [7, 8] and noninvasive [9, 10] brain stimulation is increasingly applied to cognitive dysfunction in dementia patients resulting in no to modest improvement in function and structure. There is a need to leverage the growing literature on brain stimulation’s effectiveness in mood disorders to concurrently improve depression [11] and quality of life [12] by treating neuropsychiatric symptoms that also impair quality of life such as apathy [13]. The rich literature on quality of life in AD (e.g., [2, 15]) could be leveraged to target QOL as an outcome for restorative therapies. Moving beyond symptomatic measures to real world measures of behavioral functioning (e.g., increase in pleasurable activities) could increase sensitivity and meaningfulness of therapeutic outcomes. One promising initiative is ROADMAP, a group working to develop measures of real-world functioning related to AD [16].

One important implication of stopping disease progression is the increased ambiguity about when death will occur. Without an imminent end necessary for placement in hospice, the treatment model instead will be one of palliative care. The therapy will sustain a population of people with chronic mental disability and dependence. As Watt et al. pointed out, there is a need to articulate the rights of patients and caregivers, particularly when capacity to consent is compromised, in refusing or requesting disease modifying treatments if the alternative is to allow the degenerative process to progress. In addition, there are decisions not to provide care, for example intravenous nutrition, that may change if the end of life is not imminent. Legal documents such as advanced care directives, which do not typically address decisions surrounding disease modifying treatments, may also need to be revisited.

What will be the costs of this treatment and how will disease modifying treatments alter long-term care and society? Ideally there should be less burden and financial savings from reducing new cases of AD. These funds should then be deployed to supporting existing AD patients and families with the now, prolonged, morbidity of AD. Public support for these expenditures will be important in a society that will no longer feel as personally vulnerable to AD. Those caregivers with family who developed AD prior to the treatment may need special protections. As of 2017, America will be need to support 5.7 million people with AD and that number is expected to rise to 14 million by 2050 [17]. At a current estimated lifetime cost of $329,360 per patient [18], the cost of sustaining these patients is about $1.9 trillion without factoring in changes in disease progression. The costs to caregivers and employers in time away from work will also be prolonged. Family caregivers who assume the financial burden of care, are already more likely to experience poverty later in life [19], a trend which is more likely to occur with life-extending therapies. In the US nursing home care costs almost $100,000/year [20], a burden often assumed by the government via Medicare, but only after other assets are depleted. Long-term care may also need to change over time since currently half of nursing home residents have AD or other dementias [21]. Whether disease modifying therapies are time limited versus chronic or involve expertise beyond pill dispensing may strongly shape long-term care. For example, if these treatments are administered intravenously, as in the case of the A4 study treatment, Solanezumab, there may need to be a stronger medical support across the spectrum of care in settings such as assisted living communities.

Decisions about what makes life worth living toward the end of life are evolving so that having a point of futility in treatment may relieve us as a society of the guilt and responsibility of decision making. What if there is choice in which patients receive disease modifying treatments? Will the irascible, demanding parent or the patient without an advocate-caregiver receive equal opportunities? This current futility in treatment also robs us of the gift of those precious minutes of having our loved one. If the caregiver wants the patient to live but the patient is virtually nonresponsive, will society limit which patients receive treatment based on level of dependence to save costs? The choices may be difficult, particularly if the treatment is incompletely effective and restorative treatments provide only modest improvements. What patients and family caregivers value in quality of life may be deeply personal. Identifying who makes the decisions and when becomes increasingly important as decisions surrounding prolonging a life, enhancing the quality of a life, and letting a life go become more intentional.