Alzheimer's Set to Skyrocket

Batya Swift Yasgur, MA, LSW

December 11, 2017

By 2060, an estimated 15 million Americans will have either Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI), a dramatic increase over the 6.08 million currently affected by these conditions, new research shows.

Approximately 47 million Americans currently have preclinical AD. That number is expected to jump to more than 75 million by 2060.

Researchers at the University of California, Los Angeles, Fielding School of Public Health examined data from previous epidemiologic studies using a forward calculation method and found that close to 6 million Americans will have MCI and more than 9 million will have AD dementia by 2060.

"This is the first time that these numbers regarding preclinical and clinical disease have been produced and to examine primary and secondary prevention," said Ron Brookmeyer, PhD, professor of biostatistics and the study's lead author.

"We are now able to begin understanding the different stages of Alzheimer's and the role of preclinical disease, which is important because resources needed to care for patients vary considerably over the course of the illness, from less intensive during early clinical stages to an intensive level of care equivalent to that provided by nursing homes," he told Medscape Medical News.

The study was published online December 7 in Alzheimer's and Dementia.

Degenerative Continuum

There have been significant strides in understanding the pathogenesis of preclinical AD and the role of preclinical disease, the authors write.

The diagnosis of preclinical disease "is potentially important, because persons may be more likely to benefit from disease-modifying treatments if interventions occur before the occurrence of significant brain damage," they state.

The AD process typically starts with asymptomatic amyloidosis detectable by biomarkers on positron-emission tomography amyloid imaging or by testing of cerebrospinal fluid.

After the onset of amyloidosis, the disease progresses to neurodegeneration, subtle cognitive decline, onset of MCI due to AD, and, ultimately, clinical AD dementia.

To investigate disease progression and prevalence, the researchers used a multistate model consisting of eight preclinical or clinical disease stages plus the death state. The states before MCI onset were termed "preclinical."

The researchers applied a Markov model to the data to link the calendar year to the transition rates from one state to another state.

They used data from large cohort studies to analyze preclinical and clinical transition rates. They also analyzed US background death rates by age, sex, and calendar year.

Additionally, they considered the potential impact of two types of disease-modifying preventive interventions: primary prevention, designed to be implemented before the occurrence of brain pathology; and secondary prevention, designed to slow progression from MCI to AD dementia in people who already have brain pathology.

"Understanding the process of disease progression can potentially enable us to work at all points along the continuum, along the transitions from one state to another," Dr Brookmeyer commented.

Preclinical Disease More Prevalent

In 2017, there were 3.65 million persons with clinical AD in the United States (range, 1.70 - 7.62 million). Of these, 42% (1.54 million) had late-stage clinical AD that required nursing home–level care.

It is estimated that by 2060, this number will have mushroomed to 9.30 million (range, 4.60 - 17.82 million).

In 2017, 2.43 million persons in the United States have MCI due to AD (range, 1.41 - 4.02 million); it is expected that by 2060, that will have grown to 5.70 million (range, 3.61 - 8.34 million).

In 2017, 6.08 million Americans (range, 3.11 - 11.64 million) were in one of the clinical disease states (MCI due to AD, early clinical AD, or late clinical AD), a number that is expected to jump to 15.0 million by 2060.

Close to half a million Americans (n = 46.7 million) were in one of the preclinical AD states (range, 36.23 - 57.79 million), with 22.14 million having amyloidosis, 8.33 million having neurodegeneration only, and 16.23 million having amyloidosis plus neurodegeneration.

The number of persons with preclinical AD is expected to increase to 75.68 million by 2060.

More than half of those persons currently living with only amyloidosis are younger than 70 years.

The prevalence of AD pathology is highest among patients who only have amyloidosis, followed by neurodegeneration, amyloidosis and neurodegeneration, MCI due to AD, early-stage clinical AD, and late-stage clinical AD.

The vast majority of individuals with some type of AD pathophysiology are in a preclinical state; only a small percentage (11.5%) are in a clinical state.

"I would like to emphasize that the 46.7 million Americans who have some evidence of preclinical disease may not progress during their lifetimes to either MCI or AD dementia," Dr Brookmeyer stressed.

Prevention Key

The potential impact of primary and secondary preventive strategies can be substantial. A primary prevention that reduces annual risk for onset of amyloidosis by 50% would decrease the prevalence of MCI and AD by 0.69 million and 2.35 million, respectively, in 2060.

A secondary prevention to reduce annual risk for progression to MCI by 50% would decrease the prevalence of MCI and AD by 2.14 million and 3.84 million, respectively.

"One of the big advances in the understanding of AD dementia is that it takes decades or more to progress from preclinical asymptomatic to mild MCI symptoms to AD dementia. Preventive strategies can be implemented during that time," Dr Brookmeyer said.

He noted that the increase in the incidence of clinical disease from 2017 to 2060 will be driven by the aging of the population.

"Slowing disease progression may not be a cure or magic bullet, it but may be adequate to have huge public health impact, because if you can slow disease progression, the natural lifespan of individuals may not be long enough for them to develop clinical disease," Dr Brookmeyer said.

Secondary interventions are equally important. "Even if we had primary preventions right now to stop any brain changes from occurring, there are still millions of people who already have preclinical changes, and it will be decades before we see the benefits of primary prevention because of the large number of people already in the pool," he said.

Window of Opportunity

Commenting on the study for Medscape Medical News, Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer's Association, urged the public not to "read too much into the study and feel panic."

"Although these are large numbers and we think of them as alarming, which in some sense they are, most people in preclinical stages will not go on to get AD," he emphasized.

He likened the use of biomarkers of preclinical AD to biomarkers such as cholesterol for cardiovascular disease.

"There are many people with high cholesterol who will never go on to have a heart attack."

Knowing that people with high cholesterol are at risk for a heart attack "enables us to treat them and use preventive measures, which have saved millions of lives. This study suggests that there may be a similar window of opportunity to prevent AD."

He pointed to epidemiologic studies suggesting that people with midlife obesity and classic cardiovascular risk factors are more likely to develop dementia than those without these factors.

"Some of the same interventions helpful in preventing heart disease, such as healthier diet and exercise and, potentially, the same medications, may also be protective against developing AD, in addition to social and cognitive stimulation."

He noted that the Alzheimer's Association is launching a large clinical trial in 2018 to test whether a multimodal lifestyle may reduce dementia risk in high-risk individuals.

Dr Brookmeyer added that addressing cardiovascular risk factors might have a synergistic effect in preventing overall dementia. "The present study did not analyze dementia due to causes other than AD, but it is possible that individuals with AD risk factors and vascular dementia progress more quickly from preclinical to clinical disease."

He emphasized that the decision to be screened for preclinical disease is "highly individual, based on age and other risk factors," and must be reached after discussion between clinicians, patients, and families.

The study was funded by a grant from the National Institutes of Health. Dr Brookmeyer receives fees from Takeda Inc for serving as a member of a safety monitoring board. The other authors have disclosed no relevant financial relationships.

Alzheimer's Dement. Published online December 7, 2017. Abstract

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