- Email: [email protected]
The Colombian Alzheimer's Prevention Initiative (API) Registry
Alzheimer’s & Dementia - (2016) 1-4 1 2 Research News 3 4 5 6 7 a, a a a a 8Q4 a a a a a 9 10 a a a a 11 a a a a b 12 13 c b,d,e c b,d,e,f a 14 a 15Q1 University of Antioquia, Medellin, Colombia b 16 Banner Alzheimer’s Institute, Phoenix, AZ, USA c 17 Genentech, San Francisco, CA, USA d 18 University of Arizona, Tucson, AZ, USA e 19 Arizona State University, Tempe, AZ, USA f 20 Translational Genomics Research Institute, Phoenix, AZ, USA 21 22 23 Summary The Colombian Alzheimer’s Prevention Initiative (API) Registry is a collaborative project among 24 the Neurosciences Group of Antioquia, the Banner Alzheimer’s Institute, and Genentech. The main 25 goal is to provide a source of interested research participants and data to support the API-Colombia 26 Autosomal Dominant Alzheimer’s Disease Trial and help find treatments to delay or prevent the clin27 28 ical onset of Alzheimer’s disease. 29 30 Keywords: Autosomal dominant Alzheimer’s disease; Alzheimer’s prevention initiative; Registry 31 32 33 34 35 Antioquia, the Banner Alzheimer’s Institute, Genentech, 1. Introduction 36 37 and other key partners. As the number of AD-related Alzheimer’s disease (AD) is the most common cause 38 research studies continues to expand, there is a need to 39 of dementia and poses a significant public health and rapidly communicate with and screen large numbers of po40 financial burden for society [1,2]. Latin American tential participants, enhance prescreening activities, evaluate 41 countries face the same challenges in managing site feasibility, and build the foundation for cohort and 42 dementia as wealthier countries do, but with relatively 43 biomarker studies and clinical trials [2]. One of the main less preparedness and awareness [3]. There is an urgent 44 goals of API [4,5] is to support and expand AD prevention 45 need to implement a healthcare strategy that meets the registries. 46 needs of individuals with dementia and their caregivers 47 [3] and to promote AD research. Latin American coun48 2. Registry tries can contribute to the understanding of AD by con49 ducting their own research and collaborating with 50 Since 1984, GNA has been following the world’s largest 51 international partners. known autosomal dominant Alzheimer’s disease (ADAD) 52 The Alzheimer’s Prevention Initiative (API) is an internakindred, originated from a single founder [6] and located 53 tional collaborative research program involving the Neuro54 predominantly in the region of Antioquia [7]. The Colom-
The Colombian Alzheimer’s Prevention Initiative (API) Registry
Silvia Rios-Romenets *, Hugo Lopez , Liliana Lopez , Liliana Hincapie , Amanda Saldarriaga , Lucia Madrigal , Francisco Piedrahita , Alex Navarro , Juliana Acosta-Uribe , Laura Ramirez , Margarita Giraldo , Natalia Acosta-Baena , Sebastian Sanchez , Claudia Ramos , Claudia Mu~ noz , Ana Baena , Diana Alzate , Paula Ospina , Jessica B. Langbaum , William Cho , Pierre N. Tariot , Robert Paul , Eric M. Reiman , Francisco Lopera
science
Q2
Group
of
Antioquia
(GNA)/University
*Corresponding author. Tel.: 157 42196655; Fax: ---. E-mail address: [email protected]
of
bian API Registry was formally launched in 2010. The main goal is to locate, enroll, genotype, perform medical and cognitive evaluations of Presenilin1 (PSEN1) E280A family members, and provide a resource for the
http://dx.doi.org/10.1016/j.jalz.2016.09.010 1552-5260 NWS 5.4.0 DTD JALZ2302_proof 28 October 2016 12:39 pm ce
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S. Rios-Romenets et al. / Alzheimer’s & Dementia - (2016) 1-4
API-Colombia ADAD trial (NCT01998841), other AD preclinical trials, and for biomarker, clinical, and cognitive studies of ADAD. Anyone with early-onset, potentially familial AD and healthy relatives, age 8 and older, is eligible to participate in the Colombian API Registry. Priority is given to children and grandchildren of people with AD. All interested individuals have introductory meetings about the Registry and sign written informed consent forms approved by the Comite de Bioetica de la Sede de Investigacion Universitaria, Universidad de Antioquia. Legally authorized representatives provide informed consent for minors and cognitively impaired individuals. Registrants have at least one general medical and neurological evaluation, cognitive assessment, and genetic testing and are identified as being part of a new or existing pedigree. Registrants are blind to their genetic status, except for those with symptomatic AD. All healthy relatives of affected carriers are invited for evaluation via the Registry. After enrolment, Registrants are called for periodic evaluations. All Registrants who develop mild cognitive impairment (MCI) or dementia are followed at least annually. Patients with advanced dementia or living in remote regions are offered home visits. An interdisciplinary GNA team provides basic medical care and medical education to the patient and caregiver, regardless of their participation in any research trials. In addition, the team collects missing information about other family members, contact details, and collects blood samples for genetic testing as necessary.
dementia was performed at another neurological center with the goal of finding new cases. Starting in January 2015, GNA began implementing a variety of media strategies with the main goal to inform communities about the existence of ADAD in Colombia, the importance of the Colombian API Registry, and to invite people to participate if they have a history of familial and earlyonset AD-like symptoms. These outreach strategies include letters to medical professionals, press conferences for national and international media, meetings with universities, and awareness talks. GNA has created advertisements and own Web site (http://www.quenoseteolvideayudar.com/), participated in media activities (radio, TV, and newspapers), and filmed international documentaries. GNA has promoted a social network/digital media campaign including collaboration with Lumos Labs. All interested people are contacted by a GNA member by telephone to determine if they are eligible, using criteria for selection for the Colombian API Registry (i.e., comes from a family with early-onset dementia [before 65 years] and familial aggregation). If the person or his/her family meets these criteria, GNA offers genetic testing of the family member with symptomatic AD or at least two first-degree asymptomatic relatives. If the genetic test is positive for the PSEN1 E280A mutation, the patient and/or close relatives are invited to participate in the Colombian API Registry. Families with affected members can send their blood sample to GNA for genotyping. 4. Data collection
3. Outreach and recruitment strategies GNA team uses several strategies including town visits of local hospitals, police stations, churches, town halls, and patients’ homes in Antioquia and other parts of Colombia, expanding systematic pedigree reviews and contacting missing family members. GNA members also review parish baptism, birth and marriage certificates, and burial records, to complement the information obtained via other means about existing pedigrees. Using these strategies, GNA reconstructed the branches of extensive pedigrees of PSEN1 E280A families. Review of existing PSEN1 E280A pedigrees and contact of missing family members is accomplished by members of GNA. Those who can be contacted by telephone are invited to GNA for evaluation. When a new symptomatic patient tested positive for the PSEN1 E280A mutation has been identified, the team looks for previously registered members of families and/or pedigrees to try to connect them with existing families. If the patient is not related to registered families, GNA obtains the contact information of patient family members, asks about the town in which the patient was born, and obtains a family history. Using this approach, GNA connects new families with existing families or registers a new family with the PSEN1 E2080A mutation. In addition, an extensive chart review of all cases of patients with a history of early-onset and familiar
GNA created its own secure and closed information system (SISNE, http://neurociencias.udea.edu.co), to manage extensive information including demographics, medical, neurological, and neuropsychological evaluations to support various research projects involving PSEN1 E280A families. In addition, GNA created a database of pedigrees, using Cyrillic (Cherwell Scientific, Acton, MA, USA) and Progeny (Ambry Genetics, Aliso Viejo, CA, USA) genetic pedigree software of all registered families. The information is captured using a Web application and Postgres Database (http://www.postgresql.org/). 5. Progress of the Colombian API Registry By March 2016, GNA managed the neurological and neuropsychological data of .5000 [4,7,8] of whom are members of 25 PSEN1 E280A families. Since the Colombian API Registry started in March 2010, a total of 5043 participants have been enrolled, 3904 are noncarriers, and 1119 are carriers (22.18% of the kindred), including 1065 living carriers (Fig. 1). Most of the registered carriers and noncarriers are 10–24 years old with the largest registered group in the age range of 15–19 years; almost half (518 individuals) of all registered carriers are ,30 years (Table 1). The distribution of 1065 living carriers is 901
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S. Rios-Romenets et al. / Alzheimer’s & Dementia - (2016) 1-4 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310
3
Table 1 Distribution by age in carriers and noncarriers who are alive (up to end of March 2016)
Fig. 1. The Colombian Alzheimer’s Prevention Initiative Registry: PSEN1 E280A population, 25 families, and 5043 members (up to end of March 2016).
cognitively unimpaired (cognitively normal and pre-MCI stage [8]), 8 MCI because of AD [9,10], and 156 dementia because of AD [11] and the distribution of 3889 living noncarriers is 3872 cognitively unimpaired, 4 MCI, and 13 dementia because of causes other than AD or because of late-onset sporadic AD. The most effective strategy for identification of new family members, reconstruction of branches, and expansion of existing pedigrees has been the identification of participants through parish baptism, birth, marriage certificates, burial records, and in-the-field interviews complementing thorough and repeated pedigree review. The most effective strategy for finding new families have been the media strategies as TV advertisements on popular channels, news programs, and short TV reports for general audiences. Raising awareness and offering education about ADAD to the general community through town visits and other media strategies had an effect on the expansion of the Colombian API Registry promoting “word of mouth” expansion. Providing medical care and home visits to those suffering from AD and supporting their caregivers helped to build a close working relationships between the GNA team and PSEN1 E280A families, which also helped expansion of the Colombian API Registry. More than 1000 living carriers have been identified who could learn about and enroll in a number of studies, including studies of carriers of AD-causing mutations [6–8,12–14] and studies of functional and structural brain changes, cerebrospinal fluid and plasma biomarker measures, and cognitive and clinical characterization, in preclinical and symptomatic PSEN 1 E280A ADAD [8,13–20]. In parallel, the first six individuals with homozygous PSEN1 E280A gene mutation were identified and documented [12]. Two PSEN1 E280A carriers .70 years olds without dementia, but with MCI, were detected. A total of 60 individuals with early-onset AD, some of them with a family history, were negative for the PSEN1 E280A mutation. 6. Next steps GNA continues the Colombian API Registry expansion efforts with the goal of identifying even more PSEN1
Age
Carriers
%
Noncarriers
%
0–9 10–14 15–19 20–24 25–27 28 29 30–34 35–39 40–44 45–49 50–54 55–59 60 Plus 61 Total
21 108 129 131 78 23 28 113 97 91 93 82 40 11 20 1065
1.97 10.14 12.11 12.3 7.32 2.16 2.63 10.61 9.11 8.54 8.73 7.7 3.76 1.03 1.88 100
65 508 549 491 294 89 81 425 359 246 226 190 139 22 205 3889
1.67 13.06 14.12 12.63 7.56 2.29 2.08 10.93 9.23 6.33 5.81 4.89 3.57 0.57 5.27 100
E280A members, branches, and families to support the API-Colombia ADAD trial, other preclinical AD trials, and other studies of ADAD. In addition, GNA identified a population of young cognitively unimpaired carriers (,30 years), which enable a primary prevention study in the future. Experience and results from this ambitious program may help future recruitment efforts for AD in Colombia and offer ideas for similar programs in other Latin American countries and the rest of the world. Acknowledgments This project is a collaboration among GNA/University of Antioquia, Banner Alzheimer’s Institute and Banner Alzheimer’s Foundation, an anonymous organization, Genentech/Roche, National Institute of Aging, Colciencias, and CODI from University of Antioquia. The authors gratefully Q3 acknowledge Lumos Labs, INDEC, NOVA, Nora Tobon, Ligia Uribe, Jairo Pareja, Mario Mu~noz, Rodrigo Pardo, Diana Matallana, Andrea Giraldo, Alejandra Ruiz, Valentina Obando, and families with PSEN1 E280A mutations from Colombia. Author’s disclosure: none of the authors from GNA have any financial interests or affiliations relevant to the subject to this manuscript. Two coauthors, members of the GNA team, are relatives of registered families. William Cho and Robert Paul are full-time employees of Genentech, Inc. Jessica B. Langbaum, Pierre Tariot, and Eric Reiman do not have any direct conflicts/disclosures to report. References [1] Reiman EM, Langbaum JB, Tariot PN, Lopera F, Bateman RJ, Morris JC, et al. CAP-advancing the evaluation of preclinical Alzheimer disease treatments. Nat Rev Neurol 2016;12:56–61. [2] Saunders KT, Langbaum JB, Holt CJ, Chen W, High N, Langlois C, et al. Arizona Alzheimer’s Registry: Strategy and Outcomes of a Statewide Research Recruitment Registry. J Prev Alzheimers Dis 2014; 1:74–9.
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S. Rios-Romenets et al. / Alzheimer’s & Dementia - (2016) 1-4
[3] Manes F. The huge burden of dementia in Latin America. Lancet Neurol 2016;15:29. [4] Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, et al. Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis 2011;26 Suppl 3:321–9. [5] Reiman EM, Langbaum JB, Tariot PN. Alzheimer’s prevention initiative: a proposal to evaluate presymptomatic treatments as quickly as possible. Biomark Med 2010;4:3–14. [6] Lalli MA, Cox HC, Arcila ML, Cadavid L, Moreno S, Garcia G, et al. Origin of the PSEN1 E280A mutation causing early-onset Alzheimer’s disease. Alzheimers Dement 2014;10:S277–83. [7] Lopera F, Ardilla A, Martinez A, Madrigal L, Arango-Viana JC, Lemere CA, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA 1997;277:793–9. [8] Acosta-Baena N, Sepulveda-Falla D, Lopera-Gomez CM, Jaramillo-Elorza MC, Moreno S, Aguirre-Acevedo DC, et al. Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol 2011;10:213–20. [9] Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7:270–9. [10] Sclan SG, Reisberg B. Functional assessment staging (FAST) in Alzheimer’s disease: reliability, validity, and ordinality. Int Psychogeriatr 1992;4 Suppl 1:55–69. [11] McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:263–9.
[12] Kosik KS, Munoz C, Lopez L, Arcila ML, Garcia G, Madrigal L, et al. Homozygosity of the autosomal dominant Alzheimer disease presenilin 1 E280A mutation. Neurology 2015;84:206–8. [13] Ayutyanont N, Langbaum JB, Hendrix SB, Chen K, Fleisher AS, Friesenhahn M, et al. The Alzheimer’s prevention initiative composite cognitive test score: sample size estimates for the evaluation of preclinical Alzheimer’s disease treatments in presenilin 1 E280A mutation carriers. J Clin Psychiatry 2014;75:652–60. [14] Aguirre-Acevedo DC, Lopera F, Henao E, Tirado V, Munoz C, Giraldo M, et al. Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study. JAMA Neurol 2016;73:431–8. [15] Quiroz YT, Stern CE, Reiman EM, Brickhouse M, Ruiz A, Sperling RA, et al. Cortical atrophy in presymptomatic Alzheimer’s disease presenilin 1 mutation carriers. J Neurol Neurosurg Psychiatry 2013;84:556–61. [16] Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R, Castrillon G, et al. Hippocampal hyperactivation in presymptomatic familial Alzheimer’s disease. Ann Neurol 2010;68:865–75. [17] Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer’s disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol 2012;11:1048–56. [18] Quiroz YT, Schultz AP, Chen K, Protas HD, Brickhouse M, Fleisher AS, et al. Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A CrossSectional Study. JAMA Neurol 2015;72:912–9. [19] Fleisher AS, Chen K, Quiroz YT, Jakimovich LJ, Gutierrez Gomez M, Langois CM, et al. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study. JAMA Neurol 2015;72:316–24. [20] Langbaum JB, Fleisher AS, Chen K, Ayutyanont N, Lopera F, Quiroz YT, et al. Ushering in the study and treatment of preclinical Alzheimer disease. Nat Rev Neurol 2013;9:371–81.
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The Colombian Alzheimer’s Prevention Initiative (API) Registry
Silvia Rios-Romenets *, Hugo Lopez , Liliana Lopez , Liliana Hincapie , Amanda Saldarriaga , Lucia Madrigal , Francisco Piedrahita , Alex Navarro , Juliana Acosta-Uribe , Laura Ramirez , Margarita Giraldo , Natalia Acosta-Baena , Sebastian Sanchez , Claudia Ramos , Claudia Mu~ noz , Ana Baena , Diana Alzate , Paula Ospina , Jessica B. Langbaum , William Cho , Pierre N. Tariot , Robert Paul , Eric M. Reiman , Francisco Lopera
science
Q2
Group
of
Antioquia
(GNA)/University
*Corresponding author. Tel.: 157 42196655; Fax: ---. E-mail address: [email protected]
of
bian API Registry was formally launched in 2010. The main goal is to locate, enroll, genotype, perform medical and cognitive evaluations of Presenilin1 (PSEN1) E280A family members, and provide a resource for the
http://dx.doi.org/10.1016/j.jalz.2016.09.010 1552-5260 NWS 5.4.0 DTD JALZ2302_proof 28 October 2016 12:39 pm ce
55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109
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S. Rios-Romenets et al. / Alzheimer’s & Dementia - (2016) 1-4
API-Colombia ADAD trial (NCT01998841), other AD preclinical trials, and for biomarker, clinical, and cognitive studies of ADAD. Anyone with early-onset, potentially familial AD and healthy relatives, age 8 and older, is eligible to participate in the Colombian API Registry. Priority is given to children and grandchildren of people with AD. All interested individuals have introductory meetings about the Registry and sign written informed consent forms approved by the Comite de Bioetica de la Sede de Investigacion Universitaria, Universidad de Antioquia. Legally authorized representatives provide informed consent for minors and cognitively impaired individuals. Registrants have at least one general medical and neurological evaluation, cognitive assessment, and genetic testing and are identified as being part of a new or existing pedigree. Registrants are blind to their genetic status, except for those with symptomatic AD. All healthy relatives of affected carriers are invited for evaluation via the Registry. After enrolment, Registrants are called for periodic evaluations. All Registrants who develop mild cognitive impairment (MCI) or dementia are followed at least annually. Patients with advanced dementia or living in remote regions are offered home visits. An interdisciplinary GNA team provides basic medical care and medical education to the patient and caregiver, regardless of their participation in any research trials. In addition, the team collects missing information about other family members, contact details, and collects blood samples for genetic testing as necessary.
dementia was performed at another neurological center with the goal of finding new cases. Starting in January 2015, GNA began implementing a variety of media strategies with the main goal to inform communities about the existence of ADAD in Colombia, the importance of the Colombian API Registry, and to invite people to participate if they have a history of familial and earlyonset AD-like symptoms. These outreach strategies include letters to medical professionals, press conferences for national and international media, meetings with universities, and awareness talks. GNA has created advertisements and own Web site (http://www.quenoseteolvideayudar.com/), participated in media activities (radio, TV, and newspapers), and filmed international documentaries. GNA has promoted a social network/digital media campaign including collaboration with Lumos Labs. All interested people are contacted by a GNA member by telephone to determine if they are eligible, using criteria for selection for the Colombian API Registry (i.e., comes from a family with early-onset dementia [before 65 years] and familial aggregation). If the person or his/her family meets these criteria, GNA offers genetic testing of the family member with symptomatic AD or at least two first-degree asymptomatic relatives. If the genetic test is positive for the PSEN1 E280A mutation, the patient and/or close relatives are invited to participate in the Colombian API Registry. Families with affected members can send their blood sample to GNA for genotyping. 4. Data collection
3. Outreach and recruitment strategies GNA team uses several strategies including town visits of local hospitals, police stations, churches, town halls, and patients’ homes in Antioquia and other parts of Colombia, expanding systematic pedigree reviews and contacting missing family members. GNA members also review parish baptism, birth and marriage certificates, and burial records, to complement the information obtained via other means about existing pedigrees. Using these strategies, GNA reconstructed the branches of extensive pedigrees of PSEN1 E280A families. Review of existing PSEN1 E280A pedigrees and contact of missing family members is accomplished by members of GNA. Those who can be contacted by telephone are invited to GNA for evaluation. When a new symptomatic patient tested positive for the PSEN1 E280A mutation has been identified, the team looks for previously registered members of families and/or pedigrees to try to connect them with existing families. If the patient is not related to registered families, GNA obtains the contact information of patient family members, asks about the town in which the patient was born, and obtains a family history. Using this approach, GNA connects new families with existing families or registers a new family with the PSEN1 E2080A mutation. In addition, an extensive chart review of all cases of patients with a history of early-onset and familiar
GNA created its own secure and closed information system (SISNE, http://neurociencias.udea.edu.co), to manage extensive information including demographics, medical, neurological, and neuropsychological evaluations to support various research projects involving PSEN1 E280A families. In addition, GNA created a database of pedigrees, using Cyrillic (Cherwell Scientific, Acton, MA, USA) and Progeny (Ambry Genetics, Aliso Viejo, CA, USA) genetic pedigree software of all registered families. The information is captured using a Web application and Postgres Database (http://www.postgresql.org/). 5. Progress of the Colombian API Registry By March 2016, GNA managed the neurological and neuropsychological data of .5000 [4,7,8] of whom are members of 25 PSEN1 E280A families. Since the Colombian API Registry started in March 2010, a total of 5043 participants have been enrolled, 3904 are noncarriers, and 1119 are carriers (22.18% of the kindred), including 1065 living carriers (Fig. 1). Most of the registered carriers and noncarriers are 10–24 years old with the largest registered group in the age range of 15–19 years; almost half (518 individuals) of all registered carriers are ,30 years (Table 1). The distribution of 1065 living carriers is 901
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S. Rios-Romenets et al. / Alzheimer’s & Dementia - (2016) 1-4 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310
3
Table 1 Distribution by age in carriers and noncarriers who are alive (up to end of March 2016)
Fig. 1. The Colombian Alzheimer’s Prevention Initiative Registry: PSEN1 E280A population, 25 families, and 5043 members (up to end of March 2016).
cognitively unimpaired (cognitively normal and pre-MCI stage [8]), 8 MCI because of AD [9,10], and 156 dementia because of AD [11] and the distribution of 3889 living noncarriers is 3872 cognitively unimpaired, 4 MCI, and 13 dementia because of causes other than AD or because of late-onset sporadic AD. The most effective strategy for identification of new family members, reconstruction of branches, and expansion of existing pedigrees has been the identification of participants through parish baptism, birth, marriage certificates, burial records, and in-the-field interviews complementing thorough and repeated pedigree review. The most effective strategy for finding new families have been the media strategies as TV advertisements on popular channels, news programs, and short TV reports for general audiences. Raising awareness and offering education about ADAD to the general community through town visits and other media strategies had an effect on the expansion of the Colombian API Registry promoting “word of mouth” expansion. Providing medical care and home visits to those suffering from AD and supporting their caregivers helped to build a close working relationships between the GNA team and PSEN1 E280A families, which also helped expansion of the Colombian API Registry. More than 1000 living carriers have been identified who could learn about and enroll in a number of studies, including studies of carriers of AD-causing mutations [6–8,12–14] and studies of functional and structural brain changes, cerebrospinal fluid and plasma biomarker measures, and cognitive and clinical characterization, in preclinical and symptomatic PSEN 1 E280A ADAD [8,13–20]. In parallel, the first six individuals with homozygous PSEN1 E280A gene mutation were identified and documented [12]. Two PSEN1 E280A carriers .70 years olds without dementia, but with MCI, were detected. A total of 60 individuals with early-onset AD, some of them with a family history, were negative for the PSEN1 E280A mutation. 6. Next steps GNA continues the Colombian API Registry expansion efforts with the goal of identifying even more PSEN1
Age
Carriers
%
Noncarriers
%
0–9 10–14 15–19 20–24 25–27 28 29 30–34 35–39 40–44 45–49 50–54 55–59 60 Plus 61 Total
21 108 129 131 78 23 28 113 97 91 93 82 40 11 20 1065
1.97 10.14 12.11 12.3 7.32 2.16 2.63 10.61 9.11 8.54 8.73 7.7 3.76 1.03 1.88 100
65 508 549 491 294 89 81 425 359 246 226 190 139 22 205 3889
1.67 13.06 14.12 12.63 7.56 2.29 2.08 10.93 9.23 6.33 5.81 4.89 3.57 0.57 5.27 100
E280A members, branches, and families to support the API-Colombia ADAD trial, other preclinical AD trials, and other studies of ADAD. In addition, GNA identified a population of young cognitively unimpaired carriers (,30 years), which enable a primary prevention study in the future. Experience and results from this ambitious program may help future recruitment efforts for AD in Colombia and offer ideas for similar programs in other Latin American countries and the rest of the world. Acknowledgments This project is a collaboration among GNA/University of Antioquia, Banner Alzheimer’s Institute and Banner Alzheimer’s Foundation, an anonymous organization, Genentech/Roche, National Institute of Aging, Colciencias, and CODI from University of Antioquia. The authors gratefully Q3 acknowledge Lumos Labs, INDEC, NOVA, Nora Tobon, Ligia Uribe, Jairo Pareja, Mario Mu~noz, Rodrigo Pardo, Diana Matallana, Andrea Giraldo, Alejandra Ruiz, Valentina Obando, and families with PSEN1 E280A mutations from Colombia. Author’s disclosure: none of the authors from GNA have any financial interests or affiliations relevant to the subject to this manuscript. Two coauthors, members of the GNA team, are relatives of registered families. William Cho and Robert Paul are full-time employees of Genentech, Inc. Jessica B. Langbaum, Pierre Tariot, and Eric Reiman do not have any direct conflicts/disclosures to report. References [1] Reiman EM, Langbaum JB, Tariot PN, Lopera F, Bateman RJ, Morris JC, et al. CAP-advancing the evaluation of preclinical Alzheimer disease treatments. Nat Rev Neurol 2016;12:56–61. [2] Saunders KT, Langbaum JB, Holt CJ, Chen W, High N, Langlois C, et al. Arizona Alzheimer’s Registry: Strategy and Outcomes of a Statewide Research Recruitment Registry. J Prev Alzheimers Dis 2014; 1:74–9.
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