Effective interventions to prevent, delay, and treat Alzheimer’s disease are urgently needed. Today, research reports estimate that as many as 5.1 million Americans may have the disorder, and the number is expected to rise as the population ages.
From a public health standpoint, preparing for the human, financial, and societal challenges of Alzheimer’s disease requires a clear grasp of the numbers involved—how many people are currently affected by Alzheimer’s, how prevalence may vary in different socioeconomic groups, and likely future trends. For example, an important topic for researchers has been to estimate the proportion of the aging population who will develop Alzheimer’s disease (as opposed to “normal” age-related cognitive decline) and to describe features that distinguish the two groups.
- Outlook for Individuals with Mild Cognitive Impairment
- Dementia Among the “Oldest Old”
- Focus on New Neuropathological Criteria for Alzheimer’s Disease
People with mild cognitive impairment, or MCI, have cognitive deficits that are more pronounced than is typical for their age group, but less severe than those with Alzheimer’s dementia. While MCI can be a precursor to Alzheimer’s disease, it is unclear how many people with MCI will go on to develop dementia.
To address this question, University of Pittsburgh researchers led a study involving nearly 2,000 volunteers age 65 or older living in a western Pennsylvania community (Ganguli et al., 2011). They found that only a small proportion of those who met the diagnostic criteria for MCI progressed to dementia over the course of 1 year; the majority remained stable, and a few even improved.
This image shows areas of brain susceptible to Alzheimer’s disease, such as the hippocampus.
Courtesy of Paul M. Thompson, PhD, and Arthur W. Toga, PhD, Laboratory of Neuro Imaging, UCLA.
These results differ from previous findings in clinical research settings, perhaps because people who seek clinical diagnosis and care for MCI (either on their own or at the behest of family members) may already be on the way to developing dementia. MCI in the general community may spring from a greater variety of causes that can be treated or managed, such as depression or side effects from medications. The study also showed that MCI is more likely to progress to dementia when a person has specific memory impairment and/or more than one impaired cognitive domain.
Alzheimer’s disease has a long “prodromal” phase, during which people begin to experience cognitive changes that herald the onset of the more severe stages of the disorder. To better understand this early stage, researchers at Rush University Medical Center, Chicago, followed for up to 16 years more than 2,000 older volunteers participating in two ongoing studies, the Religious Orders Study and the Rush Memory and Aging Project (Wilson et al., 2011).
They found that the 462 volunteers who eventually developed Alzheimer’s showed accelerated decline in multiple areas of cognitive function (memory, visuospatial skills, and perceptual processing) during the 5 to 6 years before receiving a diagnoses of Alzheimer’s disease. In contrast, little evidence of cognitive decline was seen in the larger group of participants who remained free of the disease.
This study suggests that declines in cognitive function are detectable well before the onset of Alzheimer’s dementia, and that changes in cognition are not an inevitable consequence of aging. Further, it suggests that treatments, once available, may be most effective if started early—underscoring the need for biological and behavioral markers to aid in early detection.
The oldest old (people age 90 or over) are the fastest growing age group in the United States. University of California, Irvine, researchers studied dementia rates among 395 participants (average age, 93) in the 90+ Study, a large study of a southern California retirement community (Peltz et al., 2011). Each year, more than 8 percent of the cognitively normal participants developed dementia. For those with MCI or other cognitive problems, the conversion rate was as high as 40 percent. The results of this study suggest that the oldest old, particularly those with MCI, have very high rates of dementia and will present a growing public health burden over the next decades.
Currently, Alzheimer’s disease is usually diagnosed in two ways. The first is by clinical examination of patients, including tests of cognitive abilities such as memory, problem solving, attention, and language. The second is by neuropathological examination after death, in which brain tissue is examined under the microscope for characteristic signs of disease such as plaques and tangles. In April 2011, the clinical diagnostic criteria for Alzheimer’s disease were revised for the first time in 27 years by a series of expert panels convened by National Institute on Aging and the Alzheimer’s Association. The new clinical criteria incorporate a deeper understanding of Alzheimer’s disease, recognizing that the symptoms of the disease develop gradually over many years. The new clinical guidelines describe the earliest preclinical stages of the disease, as well MCI and dementia due to Alzheimer’s pathology. For more on the updated guidelines, go to www.nia.nih.gov/research/dn/alzheimers-diagnostic-guidelines .
In late 2011, the neuropathology guidelines for Alzheimer’s disease—in use since 1997—were similarly updated to reflect advances in diagnosing the disorder in brain tissue. The new guidelines incorporate a new understanding of the relationship between the clinical and neuropathological signs of the disease. In contrast to the old guidelines, the new ones no longer require that individuals receive a diagnosis of dementia while living in order for their brains to be examined for signs of Alzheimer’s disease after death. This change reflects the realization in recent years that the brains of many cognitively normal older individuals contain significant amounts of amyloid plaque, which may represent the early stages of Alzheimer’s disease.
In the new guidelines, inspection of brain tissue for the presence of plaques and tangles remains central to diagnosis. However, the guidelines now ask pathologists to report in more detail the amounts and locations of plaques and tangles within the brain, and to check for them even in the brains of people who appeared free of dementia while living.
The new guidelines also require that brains be examined for signs of other diseases that may contribute to cognitive decline, such as cerebrovascular disease or Lewy body disease, and which often coexist with Alzheimer’s in the brains of older people. Finally, the new guidelines recommend that in research settings, genetic risk markers and new biomarkers be used in conjunction with neuropathological and clinical data to follow the progression of the disease and to study its underlying mechanisms (Hyman et al., 2012).