Alzheimer’s disease (AD) is the leading cause of dementia illness in the elderly and causes a significant loss of independence, productivity, and health. A new study recently published in BMC Neurology examines the expected survival of people at each stage of AD, as well as the estimated increase in the mortality risk at each stage from baseline mortality in people without cognitive impairment.

Study: Disease severity and mortality in Alzheimer’s disease: an analysis using the U.S. National Alzheimer’s Coordinating Center Uniform Data Set. Image Credit: Ground Picture / Shutterstock.com 

Introduction

About 2.4 million people died worldwide of AD and other forms of dementia in 2016, thereby making AD the fifth leading cause of death worldwide.

The aging population increases the likelihood of rising AD cases, thus causing clinicians and drug development researchers to prioritize the prevention and treatment of AD. This requires a clear understanding of mortality risk at each stage of AD, both for patient and caretaker education, as well as allow researchers to evaluate the efficacy of any proposed therapy.

Currently, the median survival for an individual diagnosed with dementia is three to seven years. Thus, a 70-year-old individual with AD suffers the loss of approximately one decade of life.

Certain confounding factors, like being a male, having severe AD, and a history of other illnesses like diabetes, hypertension, and ischemic heart disease or stroke, also affect the mortality risk of AD. Other factors that impact AD-related mortality include White ethnicity, low educational status, and low body mass, as well as being positive for apolipoprotein E ε4 in men.

The current study had a retrospective design and comprised over 12,000 people in the United States with mild to severe cognitive impairment due to AD and were over 50 years of age. Over a follow-up period of up to 15 years, researchers examined the overall survival and hazard ratios for death from all causes in these patients as compared to those with normal cognition. All data was obtained from the Uniform Data Set (UDS) of the National Alzheimer’s Coordinating Center (NACC).

What did the study show?

The participants were classified as being cognitively normal (CN), AD with mild cognitive impairment (MCI), or AD dementia. The mean follow-up in each group was about four years, four years, and two to three years, respectively.

The mean ages were higher in each of the AD cohorts as compared to the CN cohorts. Two out of three participants were female, whereas three of four were Whites of non-Hispanic origin.

People with AD who developed MCI or with dementia due to AD lived for a median of three to 12 years. Most AD patients with severe dementia died before the end of the study period.

The mortality rate increased with the severity of dementia, especially in patients of a younger age. People 65 years or older with more severe disease were seven-fold more likely to die early.

When assessed at 80 years, the risk of mortality was raised by 2.4-6.6-fold with increasing severity, thus indicating that younger participants showed a higher effect of AD severity on the risk of death. This is expected to some degree, as older participants are already at a higher risk of mortality from other potential causes of death.

However, there was no overall increase in the risk of death in the AD-MCI group as compared to those with normal cognition when adjusted for other factors that could impact the mortality risk as well as compensate for the progression of the disease over time.

Patients were more likely to die if they were older, male, lived in long-term care homes or institutions and were current smokers, alcoholics, or ever had ischemic heart disease. Being underweight or normal weight was also a risk factor, while White or Hispanic or Latino participants were at higher risk compared to Asians or non-Hispanic/Latinos.

What are the implications?

People with more severe AD are more likely to die early, with this disproportionately affecting younger individuals with AD. However, AD-MCI does not appear to carry a similar increase in risk unless it progresses to more severe cognitive impairment.

Findings might imply potential benefit of lower mortality if preventing or delaying the progression of AD is successful, and importantly, this potential benefit might be greater in relatively younger people. “

When the success of preventive and therapeutic interventions are assessed, the confounding effects of age and severity of AD must be considered to avoid false estimates of efficacy or the lack thereof.

Future studies should focus on a more general study population, unlike the present one, which included only those included in the dataset of the NACC. Finally, measures aimed at reducing the risk of daily death by slowing down or preventing the progression of AD must be evolved through clinical trials.