Page 1 Page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Page 10 Page 11 Page 12 Page 13 Page 14 Page 15 Page 16 Page 17 Page 18 Page 19 Page 20 Page 21 Page 22 Page 23 Page 24 Page 25 Page 26 Page 27 Page 28 Page 29 Page 30 Page 31 Page 32 Page 33 Page 34 Page 35 Page 36 Page 37 Page 38 Page 39 Page 40 Page 41 Page 42 Page 43 Page 44 Page 45 Page 46 Page 47 Page 48 Page 49 Page 50 Page 51 Page 52 Page 53 Page 54 Page 55 Page 56 Page 57 Page 58 Page 59 Page 60 Page 61 Page 62 Page 63 Page 64 Page 65 Page 66 Page 67 Page 68 Page 69 Page 70 Page 71 Page 72 Page 73 Page 74 Page 75 Page 76 Page 77 Page 78 Page 79 Page 80 Page 81 Page 82 Page 83 Page 84 Page 85 Page 86 Page 87 Page 88 Page 89 Page 90 Page 91 Page 92 Page 93 Page 94 Page 95 Page 96 Page 97 Page 98 Page 99 Page 100 Page 101 Page 102 Page 103 Page 104 Page 105 Page 106 Page 107 Page 10841 CHAPTER 2 | THE AGING BR AIN Risk Factors for Dementia The HRS and ADAMS are used to identify risk factors for cognitive impairment and dementia. Studies identify risk factors that may be directly modified through intervention and risk groups who may be the focus of intervention. Numerous studies use HRS and ADAMS data to contribute to our understanding of genetic and demographic risk, including educational level. A range of studies investigate medical conditions that may put indi- viduals at risk for cognitive decline. A new area of investigation is the impact of behavioral risks. Genetic and Demographic Risk With a large database of genetic information on participants, the HRS is at the forefront of dis- covery of genetic and medical risks for dementia. Research using HRS data is beginning to shed light on how genes work to affect dementia. There is likely no single memory gene, but the APOE gene, specifically the e4 variant, has been widely identified as a very significant risk factor for cognitive decline. Llewellyn et al. (2010) find that both APOE e4 and having a stroke increase the risk of dementia, but having both creates a higher level of risk that is greater than simply the sum of these two separate risks. Another study leverages the longitudinal nature of ADAMS to evaluate the contribution of the genetic marker to progression of dementia. Interestingly, APOE e4 predicts cognitive decline over time but not progression to AD (Brainerd et al. 2013). Another study creates a genetic risk score for dementia using other dementia genes and finds that more genetic risk is associated with increased risk of cognitive decline (Hayden et al. 2015). Research using HRS data has actually iden- tified a new gene that influences memory. Those with the gene FASTKD2 perform better on some memory tests than those without it. This discovery could point the way to new treatments for the memory impairments caused by AD or other age-related conditions. Although the influence of FASTKD2 is modest, it is similar to research in diabetes, cancer and hypertension that uncovered genes with similar effects that led to targets for drugs that are now commonly used (Ramanan et al. 2015). HRS research also supports the idea that memory decline is influenced by multiple genes. Marden et al. (2016) use HRS genetic data to create a polygenic risk score based on the top 22 AD-associated genes as an alternative to exclu- sively using APOE e4. The first study of prevalence in the ADAMS population shows, not surprisingly, that age is a powerful predictor of AD and other dementias. As other studies show, the APOE e4 allele is also associated with an increased risk of dementia, and a higher level of education is significantly protective. In contrast to other studies, female gender is not a predictor of Alzheimer’s risk. African Americans have an elevated risk, but FIGURE 2-4  Incidence of dementia subtype by age: 2001-2009 Source: Plassman et al. (2011). 72-79 80-89 90+ Total 18.9 (4.3) 42.2 (7.9) 82.1 (20.5) 33.3 (4.2) 938,949 1,965,362 503,009 3,407,320 72-79 80-89 90+ Total 16.6 (4.2) 24.2 (4.5) 64.0 (15.7) 22.9 (2.9) 821,592 1,127,323 392,057 2,340,972 72-79 80-89 90+ Total 39.3 (8.2) 73.1 (11.8) 206.4 (56.1) 60.4 (7.2) 1,653,503 2,538,220 630,925 4,822,649 72-79 80-89 90+ Total 102.3 (21.8) 123.8 (26.5) 124.6 (35.6) 120.3 (16.9) 741,835 1,474,533 341,135 2,557,503 Dementia Age Estimate of incidence/1,000 person-years (SE) Estimate of population incident cases Alzheimer’s disease (AD) Cognitive impairment without dementia (CIND) Dementia (among CIND) The HRS is at the forefront of discovery of genetic and medical risks for dementia. Research using HRS data is now learning more about how genes work to affect dementia.