Alzheimer's and dementia in the oldest-old: a century of challenges

Abstract

Alzheimer's disease (AD) is the most common type of dementia in the US and much of the world with rates increasing exponentially from age 65. Increases in life expectancy in the last century have resulted in a large number of people living to old ages and will result in a quadrupling of AD cases by the middle of the century. Preventing or delaying the onset of AD could have a huge impact in the number of cases expected to develop. The oldest-old are the fastest growing segment of the population and are estimated to account for 12% of the population over 65. Establishing accurate estimates of dementia and AD rates in this group is crucial for public health planning. Prevalence and incidence estimates above age 85 are imprecise and inconsistent because of the lack of very old individuals in most studies. Moreover, risk and protective factors in our oldest citizens have been studied little, and clinical-pathological correlations appear to be poor. We introduce The 90+ Study, established to address some of the unanswered questions about AD and dementia in the oldest-old. Our preliminary results show that close to half of demented oldest-old do not have known cerebral pathology to account for their cognitive deficits. Furthermore, the APOE-e4 allele appears to be a risk factor for AD only in the women in our study. In addition to the challenge of preventing and treating AD, the oldest-old will require major investigative energy to better understand the concomitants of longevity, the causes of dementia, and the factors that promote successful aging in oldest citizens.

Fig. 1

Age-Specific Incidence Rates of Alzheimer’s Disease in Studies with Oldest-Old Participants

Fig. 2

Potential Effect on Prevalence of Interventions to Delay Onset of Alzheimer’s Disease. Adapted from Brookmeyer, Gray, & Kawas [6]

Fig. 3

Estimated Life Expectancy at Birth in the United States, 1950–2003. (Source: National Vital Statistics Report [19]).

Fig. 4. Oldest-Old Population in the United States from 1950 to 2050

(Source: US Census Bureau 1950–2000, Population Projections US Census Bureau 2002 [23])

Fig. 5

Distribution of Braak & Braak Plaque and Tangle Scores for Demented and Non-Demented Participants, The 90+ Study

Fig. 6

Classification of Autopsied Participants by Clinical and Pathological Diagnosis, The 90+ Study NDIP = Not Demented Insufficient Pathology; DIP = Demented Insufficient Pathology; DAP = Demented Alzheimer Pathology