Genome-wide association studies (GWAS) avoid choosing specific candidate genesAdjusted 3MS <87, but after further neuropsychological testing and evaluation at a consensus conference (Hahs et al. 2006), individuals were determined not to be cognitively impaired. They would be classified as SA if they met other criteria. SA individuals did not have significant depressive symptoms. This study is part of the larger ongoing Collaborative Aging and Memory Project (CAMP), a multi-institutional prospective population-based study of aging and dementia in the Amish communities of Adams, Elkhart, and LaGrange counties in Indiana and Holmes County in Ohio, conducted from 2002 until the present. These communities were formed in several waves of migration in the eighteenth and nineteenth centuries (van der Walt et al. 2005). The Amish originally emigrated from Europe to Pennsylvania in the 1700s, and a further westward expansion of the Amish population occurred in the early 1800s when a subset of the Pennsylvania population migrated to Ohio and Indiana. A second wave of migration from Switzerland arrived in the nineteenth century, eventually settling in Adams County, Indiana, in the 1850s. Present-day Amish in Holmes County, Ohio, and Elkhart and LaGrange counties, Indiana are largely descended from the first wave of westward immigration from Pennsylvania, while the Adams County, Indiana settlements are largely descended from the second wave of immigration that passed through Pennsylvania (van der Walt et al. 2005). Both sets of communities have a degree of shared history and ancestry with the Pennsylvania Amish communities.

Written and informed consent was obtained for all participants and their legal guardians.

Table 1 Criteria to identify successfully aged individuals 

Criteria Test/cutoff 

Age >80 

Cognitively intact 3MS >86 (education-adjusted) 

No significant depressive symptoms GDS <6 

High function self-reported measures of 0 or 1 ADL and physical function IADL scales 0 or 1 

Nagi score 3 or 4 

Rosow Breslau score Lower extremity function >8 (12 pt scale) EPESE 

Satisfied or very satisfied with life Questionnaire 

For the SA arm of the CAMP study, individuals over age 80 were identified through public directories published by individual Amish communities and referral from individuals already enrolled in the study. Once individuals were identified, a door-to-door interview was performed for a baseline examination. Self-rated physical function was assessed by several well-established instruments. Basic self-care was assessed using a modified Katz ADL scale consisting of eight items: bathing, dressing, grooming, toileting, continence, transferring, walking, and eating (Katz 1983). Difficulty with musculoskeletal function was assessed by a five-item scale based on the work of Nagi (1976) used in the EPESE (Seeman et al. 1994): pushing large objects, stooping or kneeling, carrying weights over 10 lb, extending arms above shoulder level, and writing. Advanced daily living tasks were evaluated by a three-item modified Rosow Breslau scale (Rosow and Breslau 1966) assessing difficulty performing heavy work around the house or farm, walking up and down a flight of stairs, and walking a half mile without help. A final scale assessing more integrative functions IADLs consisted of six of the eight items suggested by Lawton and Brody (1969): traveling, shopping, preparing meals, doing housework, managing medications, and handling money.

Next, we considered whether individuals met standard cutoffs for high function on the self-reported measures of physical function: total scores of 0 or 1 on the activities of daily living (ADL) and instrumental (IADL) scales, indicating no assistance or partial assistance on only a single item needed; Nagi score of 0 or 1 (Nagi 1976), indicating no difficulty or difficulty on only one item; Rosow Breslau score of 3 or 4, indicating limitation on zero items or one item. Lower extremity function was considered by limiting SA to individuals scoring in the top 1/3 of the sample on the Established Populations for Epidemiologic Studies of the Elderly (EPESE) short physical performance battery summary score (>8 on a 12 point scale). Finally, individuals considered SA self-reported to be satisfied or very satisfied with life.

There were a total of 263 Amish individuals included in this study after performing sample quality control (QC). Among these 263 individuals, 74 were classified as SA and 189 were classified as controls. This study has been reviewed and approved by the Institutional Review Boards at the University of Miami and Vanderbilt University Medical Center.

In addition to these self-reported measures of functioning, a short physical performance test developed for use in the EPESE was used to assess lower extremity function (SeLOD scores were calculated using the Lander Green algorithm implemented in Merlin (Abecasis et al. 2002). PLINK was utilized to select a set of 4,941 markers with low linkage disequilibrium (pairwise r2<0.16 for all markers) for multipoint linkage analysis. Inter-marker map distances were obtained from the Rutgers Combined Physical Linkage Map (Matise et al. 2007). Multipoint LOD scores allowing for heterogeneity (multipoint heterogeneity LOD score (MHLOD)) were calculated using affected-only dominant (trait 0 allele frequency 0.001), affected-only recessive (trait 0 allele frequency 0.20), and nonparametric allele-sharing (multipoint nonparametric allele-sharing LOD score (MLOD*)) models.