- Cohorts by Country
- NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS)
- National Cell Repository for Alzheimer’s Disease (NCRAD)
- Alzheimer’s Disease Genetics Consortium (ADGC)
- Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE)
- International Genomics of Alzheimer’s Project (IGAP)
- National Alzheimer’s Coordinating Center (NACC)
- Centers for Common Disease Genomics (CCDGs, formerly NHGRI Large Scale Sequencing and Analysis Centers)
- The American Genome Center (TAGC)
(FUS2.0 cohorts coming soon)
The A4 Study was designed as a three-year, placebo-controlled, randomized clinical trial to test whether anti-amyloid treatment can slow the rate of cognitive decline in older individuals from diverse ethnic-racial backgrounds (non-Hispanic White, African American and Latino/Hispanic) with evidence of amyloid accumulation on screening PET scans.
The Adult Changes in Thought (ACT) study is a longitudinal prospective cohort study that began in 1994. Participants are randomly selected from Seattle area members of Group Health aged 65 years or older. Participants are cognitively intact at study enrollment, defined operationally as a CASI (Cognitive Abilities Screening Instrument) score of >85 or consensus diagnosis of “not demented” following comprehensive neurological and neuropsychological assessment. Incident cases of dementia are identified with the same 2-stage sampling scheme, where all participants with CASI scores <86 are evaluated with a comprehensive neurological and neuropsychological assessment, and all results are considered at a consensus conference. Autopsy is also available for this collection; autopsy consent rates are about 25% of the cohort. Genomic DNA from blood and/or brain tissue is available from this collection. This study includes 4690 subjects across three sub-cohorts.
ADNI is a global research study that actively supports the investigation and development of treatments that slow or stop the progression of AD. In this multisite longitudinal study, researchers at 63 sites in the US and Canada track the progression of AD in the human brain with clinical, imaging, genetic and biospecimen biomarkers through the process of normal aging, early mild cognitive impairment (EMCI), and late mild cognitive impairment (LMCI) to dementia or AD. Participants undergo a series of initial tests that are repeated at intervals over subsequent years, including a clinical evaluation, neuropsychological tests, genetic testing, lumbar puncture, and MRI and PET scans. The overall goal of ADNI is to validate biomarkers for use in Alzheimer’ s disease clinical treatment trials. 1338 cases and 483 controls are included in this study across 4 phases.
The Amish Protective Variant Study, based at Case Western Reserve University and the University of Miami (Cummings et al. 2012; D’Aoust et al. 2015), is being conducted in the Indiana and Ohio Old Order Amish (OOA) population. The OOA, an isolated founder population originating from emigration of German and Swiss Anabaptists to the U.S. in the 1700’s and 1800’s has been examined in multiple genetic studies of complex diseases including AD, age-related macular degeneration, and successful aging. With fewer than 1,000 founders and self-imposed cultural and religious isolation, the introduction of genetic variation among the OOA has been significantly restricted. Anecdotally, their agrarian lifestyle and firm behavioral norms likely have reduced variation in environmental exposures. Further, the OOA are an excellent population for genetic studies in that they have large and stable pedigrees and low variability in lifestyle factors.
Individuals included in this study have been recruited over the past 20 years for multiple studies of AD or dementia, age-related macular degeneration, and successful aging. For all these studies, the primary criteria for enrollment included being age 50 or older (AMD), age 60 or older (AD), or age 80 or older (successful aging), being part of the Amish community, and being of Amish descent. Recruitment primarily included community-based home visits. Participants were recruited from Amish families living in Holmes County, Ohio and Elkhart, LaGrange, and Adams Counties, Indiana.
Nuclear family pedigrees are provided for convenience. However, as a founder population, these Amish individuals have, on average, a genetic relationship between the equivalent of second and third cousins. Thus additional, more complex relationships exist across the nuclear pedigrees.
The ASPREE STUDY (ASPirin in Reducing Events in the Elderly) was an international, randomized, placebo-controlled trial funded by the NIH to determine whether daily low dose aspirin (100 mg) increased survival, free of dementia or physical disability, for healthy older people (>60 years of age) without a history of cardiovascular disease, dementia or significant physical disability at enrollment. It included 19,114 healthy older individuals and the initial completion was in 2018 (McNeil 2018). ASPREE-eXTension (ASPREE-XT) study, funded by the NIA, is an observational follow-up of the same cohort that will be extended from 2019 through 2024. ASPREE and ASPREE-XT has and will continue to determine factors, such as those related to lifestyle, health behavior, environment, genes, blood biomarkers and many others, that may be predictors of good health and longevity or predispose to age-related diseases, but is especially focused upon dementia and cognitive decline.
The Atherosclerosis Risk in Communities Study (ARIC), sponsored by the National Heart, Lung, and Blood Institute (NHLBI) is a prospective epidemiologic study conducted in four U.S. communities. ARIC is designed to investigate the causes of atherosclerosis and its clinical outcomes, and variation in cardiovascular risk factors, medical care, and disease by race, gender, location, and date. To date, the ARIC study has published over 2,000 articles in peer-reviewed journals. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community, to receive extensive examinations, including medical, social, and demographic data. Follow-up also occurs semi-annually, by telephone, to maintain contact and to assess health status of the cohort. In the Community Surveillance Component, the four communities are investigated to determine the long term trends in hospitalized myocardial infarction (MI) and coronary heart disease (CHD) deaths in approximately 470,000 men and women aged 35-84 years.
The Austrian Stroke Prevention Study is a community-based cohort study on the effects of vascular risk factors on brain structure and function in elderly participants without a history or signs of stroke and dementia on the inhabitants of Graz, Austria. 8193 individuals aged 50 to 75 years, stratified by sex and 5-year age groups, were randomly selected from the official community register. Overall, 2794 of the invited subjects returned a card stating their willingness to participate. Recruitment into the study was stopped after enrollment of 2000 eligible participants. They were all white and of Central European origin. Individuals were excluded from the study if they had a history of neuropsychiatric disease, including previous cerebrovascular attacks and dementia, or an abnormal neurological status determined on the basis of a structured clinical interview and a physical and neurological examination. Every fourth study participant, or in case of refusal the next participant, was invited to enter phase II of the study, which included MRI and Doppler sonography.
Description coming soon.
The Cache County Study on Memory Health and Aging (CCS) was initiated in 1994 to investigate the association of APOE genotype and environmental exposures on cognitive function and dementia. This cohort of 5092 Cache County, Utah, residents (90% of those aged 65 years or older in 1994), has been followed continuously for over 15 years, with four triennial waves of data collection and additional clinical assessments for those at high-risk for dementia. DNA samples were obtained from 97.6% of participants. The Cache County population is exceptionally long-lived and ranked number one in life expectancy among all counties in the 1990 US Census. All but one of the members of the CCS have been linked to the UPDB and their extended genealogies are known. This population was the source of most of the Centre d’Etude du Polymorphisme Humain (CEPH) families that have been used to represent Caucasians in many genetic studies worldwide, including the HapMap project. Recent analyses confirm that these data are representative of the general European-American population. For this study, we needed both AD cases and resilient individuals identified in the same pedigrees.” (Ridge, P.G., Karch, C.M., Hsu, S. et al. Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience. Genome Med 9, 100 (2017). https://doi.org/10.1186/s13073-017-0486-1)
The Cardiovascular Health Study (CHS) is an NHLBI-funded observational study of risk factors for cardiovascular disease in adults 65 years or older (n=5888, including a secondary cohort of predominately African-American subjects (n=687)). Starting in 1989, and continuing through 1999, participants underwent annual extensive clinical examinations. Measurements included traditional risk factors such as blood pressure and lipids as well as measures of subclinical disease, including echocardiography of the heart, carotid ultrasound, and cranial magnetic-resonance imaging (MRI). Examination also included cognitive measures. At six month intervals between clinic visits, and once clinic visits ended, participants were contacted by phone to ascertain hospitalizations and health status. The main outcomes are coronary heart disease (CHD), angina, heart failure (HF), stroke, transient ischemic attack (TIA), claudication, and mortality. Participants continue to be contacted by phone every 6 months.
The Case Western Reserve University (CWRU) Autopsy Cohort was an Alzheimer’s Disease Research Center (ADRC) clinic-based sample. Subjects included in the Case Western Reserve Autopsy cohort include individuals who were participants in the Brain Health and Memory Center Research Brain Donation Protocol at University Hospitals Cleveland Medical Center in Cleveland, OH. The target population is patients who have degenerative disorders of the central nervous system. Recruitment of potential subjects is primarily based on referrals from health care providers. In addition, individuals who learn of the program through other means may participate. This is an autopsy-based study designed to analyze post-mortem brain tissue. Medical records are also obtained as available to help correlate brain behavior relationships.
Participants were classified into clinical categories (Alzheimer’s disease, Controls, and other dementia (ADRD) based on description of the brain gross examination and neuropath microscopic description. Cases consisted of individuals who were diagnosed as AD. Controls consisted of individuals who had insufficient findings of neurofibrillary tangles or BRAAK stage I/II or essentially normal brain for age. Other (ADRD) consisted of individuals with diagnosis not being AD or Control.
The Case Western Reserve University (CWRU) Rapid Decline Cohort (Cohen et al. 2015) represents patients with rapid decline. Subjects included in the Case Western Reserve Rapid Decline dataset include individuals who were initially suspected of having Creutzfelt-Jakob disease (CJD). The Brains of these individuals were obtained by the National Prion Disease Pathology Surveillance Center (NPDPSC) for testing and confirmation of CJD. Samples are received from across the United States. After testing, these samples were determined not to have CJD, but to have pathology consistent with Alzheimer disease. The usual progression of CJD is quite rapid, so that the vast majority of these individuals progressed from onset to death in less than 3 years. This is an autopsy-based study designed to analyze post-mortem brain tissue. Medical records are obtained when available to help correlate brain behavior relationships.
Participants were classified as either Alzheimer’s disease or another dementia (ADRD; Lewy body Dementia, Frontotemporal dementia) based on description of the brain gross examination and neuropath microscopic description.
The Center for Cognitive Neuroscience and Aging (CNSA) at the University of Miami is a center focused on the valuation, management, treatment and care for older persons and their families with memory and other brain disorders affecting cognition.
The Chicago Healthy Aging Project (CHAP) is a longitudinal population study of an urban general population sample (n= 10,000+) lasting from 1993 to 2012 of common chronic health problems of older persons, especially of risk factors for incident Alzheimer’s disease, based in three neighborhoods on the south side of Chicago. An initial enrollment was supplemented by enrollment of successive age cohorts of community residents as they attained the age of 65. After the enrollment period, the CHAP pursued a complex strategy for follow-up evaluations, interviewing all participants about every three years and conducting in-depth clinical evaluations among a stratified random sample of participants at each of these cycles. Cognition was assessed for all CHAP subjects and the presence of Alzheimer’s disease (AD) was assessed for those in the Clinical Evaluation sample.
Clinical evaluation included a neuropsychological battery, structured neurological examination and medical history. For persons in whom there was evidence of dementia and uncertainty as to whether a stroke had occurred or its relation to detention, limited diagnostic use of brain magnetic resonance imaging (MRI) occurred. Diagnosis of dementia required loss of cognitive function by the neurologist’s assessment and impairment in two or more functions on cognitive performance tests. The diagnosis of Alzheimer’s disease was by criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) for probable Alzheimer’s disease.
Patients with a clinical Parkinsonism in life and neuropathological confirmation of Corticobasal Degeneration (CBD) were identified from brain banks, research hospitals and neuropathologists. The top three contributing sites were the Mayo Clinic, University College London, and the University of Pennsylvania and additional small numbers of cases were obtained from various other institutions across the US and some international collaborators. The neuropathological diagnosis was made according to NINDS neuropathologic diagnostic criteria. DNA was extracted from brain tissue from patients who had consented for brain donation. DNA samples and/or tissue were sent to the University of Pennsylvania for preparation for genotyping.
The Cuban American Alzheimer’s Disease Initiative (CuAADI) is a convenience sample ascertained through community outreach to Alzheimer’s and adult day care centers in Southern Florida, lay conferences, and Neurology and Memory Disorders clinics. Eligibility was based on self-reported Cuban heritage. The participants were recruited in South Florida which is home to the largest number of Cubans in the US. Most of our participants have been living in South Florida since they moved from Cuba in the last 20 to 45 years.
Participants were ascertained and evaluated through community centers, referrals from University of Miami memory clinics and adult day care centers. Some participants were evaluated in their homes. All participants greater than 60 years of age underwent a standard clinical evaluation consisting of a medical and family history interview, neuropsychological testing, behavioral and emotional assessments, and functional measures. Venous blood samples (or saliva samples when needed) were collected on all participants. All assessments were conducted in the preferred language of the participant or knowledgeable informant.
A family-based cohort study that is embedded in the Genetic Research in Isolated Populations (GRIP) program in the South West of the Netherlands. The aim of this program was to identify genetic risk factors in the development of complex disorders. For the Erasmus Rucphen Family Study (ERF), 22 families that had at least five children baptized in the community church between 1850-1900 were identified with the help of genealogical records. All living descendants of these couples and their spouses were invited to take part in the study. Data collection started in June 2002 and was finished in February 2005 (n=2065).
Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) included 683 at-risk family members from 242 AD-affected families of Caribbean Hispanic descent. These families have 2 or more individuals affected with Alzheimer’s disease. A system of recruitment was also set up in the Dominican Republic with the help of several local physicians, including the president of the Dominican Society of Geriatrics and Gerontology. All affected and unaffected family members are evaluated in person both in the Dominican Republic and New York. A case was defined as any individual meeting NINCDS-ADRDA criteria for probable or possible LOAD. The Clinical Dementia Rating was used to rate the severity of dementia. Brain imaging and other laboratory study results were reviewed, when available, to ensure full implementation of the NINCDS-ADRDA criteria.
Once patients with LOAD were identified, their illnesses were documented with standardized neurological and neuropsychological evaluations. Structured family history interviews were then conducted with available family members to determine whether patients had living siblings or relatives with the disease. Medical and neurological examinations were completed for all family members. Brains of participants with dementia and history of stroke were administered magnetic resonance imaging scans to exclude patients with comorbid cerebrovascular disease. DNA samples and cell lines are stored for all participating individuals.
The goal of this study is to root out genetic variants that increase late onset Alzheimer disease risk in this ethnic group. This study was initiated in 1998 and recruited subjects from the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain in New York as well as from clinics in the Dominican Republic.
The Framingham Heart Study, under the direction of the National Heart, Lung and Blood Institute (NHLBI), formerly known as the National Heart Institute, has been committed to identifying the common factors or characteristics that contribute to cardiovascular disease (CVD) since its beginning in 1948. FHS has followed CVD development over a long period of time in three generations of participants. The Study began in 1948 by recruiting an Original Cohort of 5,209 men and women between the ages of 30 and 62 from the town of Framingham, Massachusetts, who had not yet developed overt symptoms of cardiovascular disease or suffered a heart attack or stroke. Since that time the Study has added an Offspring Cohort in 1971, the Omni Cohort in 1994, a Third Generation Cohort in 2002, a New Offspring Spouse Cohort in 2003, and a Second Generation Omni Cohort in 2003.
Data collected over the course of FHS have included those derived from physical examinations, lifestyle interviews, detailed medical histories, and laboratory testing. DNA has been collected from blood samples for the Original, Offspring, and Third Generation Cohorts. Available phenotype information includes quantitative measures of the major CVD risk factors such as systolic blood pressure, total and HDL cholesterol, fasting glucose, and cigarette use, as well as anthropomorphic measures such as body mass index, biomarkers such as fibrinogen and CRP, and electrocardiography measures such as the QT interval.
Participants of the GenerAAtions Study were identified through the electronic claims database of the Henry Ford Health System. Community-dwelling African Americans aged 65 and older who had at least one encounter with the Henry Ford Health System in the three years prior to their recruitment and who had an available proxy informant were eligible for this study. Cases met NINCDS-ADRDA criteria for possible or probable AD, determined in a consensus conference which included a behavioral neurologist, psychiatrist, neuropsychologist, and a behavioral neurology nurse practitioner. Phenotypic data were available for 242 AD cases and 204 cognitively normal controls.
Genetic Differences (GenDiff) was an epidemiologic case control study. Cases (235) were newly recognized (e.g., “incident”) “Probable AD” (McKhann criteria NINCDS-ADRDA). Subjects were discovered and diagnosed by the Alzheimer’s Disease Patient Registry from a community based HMO. Controls were selected at random from the same HMO, without cognitive impairment, and frequency matched for age and sex. The cohort was derived from the same population as the Adult Changes in Thought (ACT) study. They were also cognitively screened and followed. Blood samples were obtained on most that entered GenDiff with consent for any future genetic analyses.
The Gwangju Alzheimer’s and Related Dementias (GARD) Cohort is a prospectively followed sample of persons in a senior citizen’s community located in the South Korean southwestern city of Gwangju. A large portion of the cohort has been evaluated with the Seoul Neuropsychological Screening Battery (SNSB) and had a brain MRI scan, and some participants have had PET-amyloid imaging. Previous studies of this cohort include GWAS for AD (Kang et al. J Alzheimers Dis. 2021; 82(4):1451-1460) and brain MRI traits (Park et al. Transl Psychiatry 2021; 11:590). Another study identified a SNP in the APOE promoter that modifies the effect of the ε4 allele and may explain differences in the AD/ε4 across East Asians, Caucasians and African Americans (Choi et al. J Clin Med 2019; 8:1236).
LASI-DAD is an in-depth study of late-life cognition and dementia. It draws a sub-sample of 4,000+ LASI respondents aged 60 and older and administers in-depth cognitive tests and informant interviews. LASI is an ongoing cohort study of 72,000 community-residing older adults aged 45 and older and their spouses regardless of age, with an oversample of persons aged 65 and above.The study design involves following all individuals who move into institutions, although that number is expected to be very small in India. Using the Census as the sampling frame, LASI is representative of both the nation as a whole and each state and union territory. Due to administrative and linguistic considerations, the fieldwork for the main LASI unfolded in three phases, and therefore the LASI-DAD fieldwork was also carried out in phases, recruiting most respondents about 6 – 7 months after the core LASI interview.
The HRS is a nationally representative sample with oversamples of African-American and Hispanic populations. The target population for the original HRS cohort includes all adults in the contiguous United States born during the years 1931–1941 who reside in households. HRS was subsequently augmented with additional cohorts in 1993 and 1998 to represent the entire population 51 and older in 1998 (b. 1947 and earlier). Since then, the steady-state design calls for refreshment every six years with a new six-year birth cohort of 51–56 year olds. This was done in 2004 with the Early Baby Boomers (EBB) (b. 1948-53) and in 2010 with the Mid Boomers (MBB) (b. 1954–59).
This data release includes respondents who consented to the saliva collection in 2006 (‘Phase 1’), 2008 (‘Phase 2’), 2010 (‘Phase 3’), and 2012 (‘Phase 4’). Thus, Phases 1 and 2 include samples from HRS panel respondents (largely b. < 1954) while Phases 3 and 4 include samples from the MBB cohort, an additional minority oversample enrolled in HRS in 2010, and panel non-responders/consenters from 2006 and 2008.
In 2007, researchers at the Scripps Research Translational Institute launched the Wellderly study in the hopes of unlocking the genetic secrets behind lifelong health. Genetic factors that protect against disease in genetically exceptional individuals have been successfully translated to drugs for the general population. This ongoing study has enrolled more than 1,400 people from across the country ranging in age from 80 to 105, who have not developed any common chronic medical conditions or diseases.
Description above lifted from the Scripps website, 12/13/22
Participants were enrolled in the Hillblom Aging Network at the University of California, San Francisco (UCSF) Memory and Aging Center. All participants underwent comprehensive neurobehavioral evaluations and met the following inclusionary criteria at baseline: 1) clinically normal based on consensus conference with a neurologist and board-certified neuropsychologist; 2) no history of neurological disorder known to impact cognition (e.g., epilepsy, stroke); and 3) functionally intact as defined by an informant-obtained CDR global score of 0 (Morris, 1993). More specifically, the determination of clinically normal by consensus conference involved ruling out the presence of mild cognitive impairment, dementia, or any other neurological condition resulting in cognitive, behavioral, motor, or functional decline (e.g., Parkinson’s disease), according to widely used diagnostic criteria (e.g., Albert et al., 2011; Armstrong et al., 2013; Gorno-Tempini et al., 2011; Höglinger et al., 2017; McKeith et al., 2017; McKhann et al., 2011; Postuma et al., 2015; Rascovsky et al., 2011). Three main sources of information were considered by the neurologist and neuropsychologist during the diagnostic conference. First, participants underwent a thorough evaluation with the neurologist that involved a comprehensive neurological examination, clinical interview, and review of systems. Second, neuroimaging (structural MRI) was reviewed to screen out gross brain pathology with potential to negatively impact cognition (e.g., tumor). Third, participants completed a battery of neuropsychological tests to objectively assess major domains of cognitive function, including attention, executive functioning, memory, language, and visuospatial skills. Cognitive impairment was defined by the presence of subjective cognitive decline, as reported by the participant or informant, together with objective performance on neuropsychological testing that was below expectation given the participant’s age and level of premorbid functioning (Albert et al., 2011). In making the determination of clinically normal, emphasis was placed on ruling out any declines in the participant’s ability to perform everyday tasks due to cognitive changes.
University of California San Francisco Alzheimer’s Disease Research Center under grant P30AG062422;
Larry L. Hillblom Network under Grant 2014-A-004-NET;
R01AG032289 (PI: JK);
R01AG048234 (PI: JK)
Espeland MA, Yassine H, Hayden KD, Hugenschmidt C, Bennett WL, Chao A, Neiberg R, Kahn SE, Luchsinger JA; Action for Health in Diabetes (Look AHEAD) Research Group. Sex-related differences in cognitive trajectories in older individuals with type 2 diabetes and overweight or obesity. Alzheimers Dement (N Y). 2021 Apr 9;7(1):e12160. doi: 10.1002/trc2.12160. PMID: 33860069; PMCID: PMC8033410.
Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH. Cognitive aging is not created equally: differentiating unique cognitive phenotypes in “normal” adults. Neurobiol Aging. 2019 May;77:13-19. doi: 10.1016/j.neurobiolaging.2019.01.007. Epub 2019 Jan 24. PMID: 30772736; PMCID: PMC6486874.
Staffaroni AM, Brown JA, Casaletto KB, Elahi FM, Deng J, Neuhaus J, Cobigo Y, Mumford PS, Walters S, Saloner R, Karydas A, Coppola G, Rosen HJ, Miller BL, Seeley WW, Kramer JH. The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed. J Neurosci. 2018 Mar 14;38(11):2809-2817. doi: 10.1523/JNEUROSCI.3067-17.2018. Epub 2018 Feb 13. PMID: 29440553; PMCID: PMC5852659.
Yokoyama JS, Sturm VE, Bonham LW, Klein E, Arfanakis K, Yu L, Coppola G, Kramer JH, Bennett DA, Miller BL, Dubal DB. Variation in longevity gene KLOTHO is associated with greater cortical volumes. Ann Clin Transl Neurol. 2015 Mar;2(3):215-30. doi: 10.1002/acn3.161. Epub 2015 Jan 26. PMID: 25815349; PMCID: PMC4369272.
The Indianapolis-Ibadan Dementia Project, established in 1991, is a longitudinal prospective population-based comparative epidemiological study of the prevalence and incidence rates and risk factors for Alzheimer’s disease and other age associated dementias. Enrollment of community-dwelling elderly (age>65 years) African Americans living in Indianapolis and Yoruba living in Ibadan, Nigeria employed the same research design, methods, and investigators (see study description at https://iidpportal.medicine.iu.edu/). The first enrollment wave began in 1992 and participants were followed every 2 to 3 years.
Participants were ascertained and evaluated through community centers, clinical and hospital settings as well in community centers and at home. All participants greater than 65 years of age who agreed to participate were screened using measures. Those who failed the screen underwent a more comprehensive clinical evaluation. Medical and family history interview, neuropsychological testing, behavioral and emotional assessments, and functional measures, including collateral informant report, were available for all most participants. Venous blood samples (were collected on all participants. All assessments were conducted in the preferred language of the participant or knowledgeable informant. Finally, all participants were adjudicated by a clinical consensus panel and were classified according to various criteria in place at the time of the clinical data collection Details on diagnosis criteria and process were described in Hendrie et al JAMA 2001.
ISAVRAD is a longitudinal study of older adult Amerindians from Northern Argentina with or without exposure to SARS-CoV-2 infection to understand the impact of interactions between ancestral genomic variants and infection on the risk of cognitive decline and ADRD. With funding from the Alzheimer’s Association and Fundacion FULTRA, 875 participants over 60 years of age and without pre-infection cognitive impairment were enrolled during the first 18 months of the pandemic; collected data include exhaustive clinical phenotypes, detailed cognitive assessments, plasma for biomarkers and WGS.
The search for novel risk factors for Alzheimer disease relies on access to accurate and deeply phenotyped datasets. The Memory and Aging Project at the Knight-ADRC (Knight ADRC-MAP) collects plasma, CSF, fibroblast, neuroimaging clinical and cognition data longitudinally and autopsied brain samples. We are using multi-tissue (brain, CSF and plasma) multi-omic data (genetics, epigenomics, transcriptomics, proteomics and metabolomics) to identify novel risk and protective variants, create new prediction models and identify drug targets. The study cohort includes MAP participants from the Knight-ADRC at Washington University in St. Louis (MO). MAP participants have to be at least 65 years old and have no memory problems or mild dementia at the time of enrollment. There is no age at onset criteria for this cohort. Cases had to have a CDR >=0.5 whereas controls had to have a CDR=0 at last assessment. AD definition is based on a combination of both clinical and pathological information if available. Pathologic diagnosis will overrule clinical diagnosis. Participants are Non-Hispanic white from North America (95%) and African American (5%). Autopsy information was provided if available, but it is not a requirement for enrollment.
Korean Brain Aging Study for the Early Diagnosis and Prediction of AD (KBASE) is a prospective cohort study launched at Seoul National University (SNU) in 2014 using a similar design and methods as the North American Alzheimer’s Disease Neuroimaging Initiative (ADNI). The KBASE cohort consists of well-characterized participants including cognitively normal (CN) controls with a wide age range (20 to 90 years) and older adults with mild cognitive impairment (MCI) or AD dementia (AD). KBASE included longitudinal collection of clinical, cognitive and lifestyle data, multimodal MRI and PET (amyloid, tau and FDG) neuroimaging, and bio-specimens in Korea during the first phase (“KBASE1”). KBASE2 represents a collaboration between the ADSP, Indiana University, the KBASE team at SNU, USC/LONI and UPENN. Over 1000 whole genome sequences (WGS) of Korean participants will be contributed to the ADSP, and the extensive ADSP multi-ethnic data set will be analyzed. KBASE2 will expand the cohort and continue longitudinal data and sample collection and provide WGS and data harmonization and sharing, analyze longitudinal amyloid, tau, neurodegeneration and vascular (A/T/N/V) imaging biomarkers and analyze multi-omics data for association with A/T/N/V biomarkers for AD to identify dysregulated gene modules and pathways.
The LonGenity study at Albert Einstein College of Medicine has been recruiting community dwelling Ashkenazi Jewish seniors aged 65 or older in the United States since 2008. Offspring of Parents with Exceptional Longevity (OPEL), defined by having at least one parent who lived to age 95 or older and Offspring of Parents with Usual Survival (OPUS), defined by having neither parent survived to age 95 are being followed annually in this longitudinal study. The goal of this study is to search for longevity genes that may act to slow the aging process and/or protect from age-related diseases. Participants undergo comprehensive cognitive testing, physical performance assessments, and complete medical and family history questionnaires at annual visits. Blood samples are collected biennially and are used for DNA analysis. Participants selected for this sub-study were either (1) age ³70, carriers of APOe4/e4 genotype, and exhibited normal cognitive function or (2) were age ³80, carriers of APOe3/e4 genotype, and exhibited normal cognitive function. Cognitive function was evaluated annually with comprehensive neurocognitive test battery.
Grants from the National Institutes of Health R01AG042188, R01AG044829, R01AG046949, R01AG057909, R01AG061155, P30AG038072, the Einstein-Paul Glenn Foundation for Medical Research Center for the Biology of Human Aging.
The Longevity Genes Project (LGP), established in 1998 at Albert Einstein College of Medicine, recruits Ashkenazi Jewish centenarians (age 95 and older) who are in general good health at age 95, offspring of centenarians, and spouses of offspring in the Eastern United States. The goal of this cross-sectional study is to identify longevity genes that help to slow the aging process and/or protect from age-related diseases. Participants undergo a physical examination (including physical measurements and mini mental state examination (MMSE)), complete a series of questionnaires (including medical and family history, physical activity, etc.), as well as a blood draw or cheek swab collection for DNA analysis. Participants selected for this sub-study were living in the community and were either (1) age ³70, carriers of APOe4/e4 genotype, and exhibited normal cognitive function or (2) were age ³80, carriers of APOe3/e4 genotype, and exhibited normal cognitive function. For individuals age 95 and older, normal cognitive function was defined as full MMSE score >22 or blind MMSE score ³16. Fo individuals age <95, normal cognition was defined as MMSE >25.
Grants from the National Institutes of Health R01AG042188, R01AG044829, R01AG046949, R01AG057909, R01AG061155, P30AG038072, the Einstein-Paul Glenn Foundation for Medical Research Center for the Biology of Human Aging.
All 248 cases and 98 controls consisted of Caucasian subjects from the United States ascertained at the Mayo Clinic. All subjects were diagnosed by a neurologist at the Mayo Clinic in Jacksonville, Florida or Rochester, Minnesota. The neurologist confirmed a Clinical Dementia Rating score of 0 for all controls; cases had diagnoses of possible or probable AD made according to NINCDS-ADRDA criteria. Autopsy-confirmed samples came from the brain bank at the Mayo Clinic in Jacksonville, FL and were evaluated by a single neuropathologist. In clinically-identified cases, the diagnosis of definite AD was made according to NINCDS-ADRDA criteria.
The Mexican Health and Aging Study (MHAS) is a national longitudinal study of adults 50 years and older in Mexico.
The baseline survey, with national and urban/rural representation of adults born in 1951 or earlier, was conducted in 2001 with follow-up interviews in 2003, 2012, 2015, and 2018. A new sample of adults born between 1952-1962 was added in 2012. Similarly, in 2018 a new cohort of adults born between 1963 and 1968 was added to refresh the sample.
The study is a collaborative effort among researchers from the University of Texas Medical Branch (UTMB), the Instituto Nacional de Estadística y Geografía (INEGI, Mexico), the University of Wisconsin, the Instituto Nacional de Geriatría (INGER, Mexico), the Instituto Nacional de Salud Pública (INSP, Mexico), and University of California Los Angeles (UCLA). The MHAS is partly supported by the National Institutes of Health/National Institute on Aging (R01AG018016, R Wong, PI) in the United States and the Instituto Nacional de Estadística y Geografía (INEGI) in Mexico.
Cohort description taken from the MHAS website, July 29, 2022.
Description coming soon.
Description coming soon.
The Minority Aging Research Study (MARS) is a longitudinal, epidemiological cohort study of decline in cognitive function and risk of Alzheimer’s disease in older African-Americans. MARS began in 2004 and over 600 persons have enrolled, 560 of which are currently alive. The study enrolls African-American men and women over age 65 that haven’t been diagnosed with dementia. After consent is obtained, a baseline evaluation is scheduled and performed in the participant’s home. At the baseline visit, a uniform, structured clinical evaluation is completed consisting of an interview to ascertain a variety of lifestyle and experiential risk factors, a neurological examination, a blood draw, and a comprehensive neuropsychological battery of 23 cognitive tests. The clinical evaluation is repeated on an annual basis. The autopsy program is offered to all subjects as well but not required. Participants also have yearly blood draws which result in the storage of serum, plasma and cells.
Human brains were accessed from the Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB–Mount Sinai NIH Neurobiobank) cohort, which holds over 2,040 well-characterized brains. This cohort was assembled after applying stringent inclusion/exclusion criteria and represents the full spectrum of cognitive and neuropathological disease severity in the absence of discernable non-AD neuropathology. For each sample, neuropathological assessment was performed according to the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) protocol and included assessment by hematoxylin and eosin, modified Bielschowski, modified thioflavin S, and anti-β amyloid (4G8), anti-tau (AD2) and anti-ubiquitin. A Braak AD-staging score for progression of neurofibrillary neuropathology was assigned to each case. Quantitative data regarding the mean of the density of neuritic plaques in the middle frontal gyrus, orbital frontal cortex, superior temporal gyrus, inferior parietal cortex and calcarine cortex were also collected. Clinical dementia rating scale (CDR) was conducted for assessment of dementia and cognitive status. (Wang, M., Beckmann, N., Roussos, P. et al. The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer’s disease. Sci Data 5, 180185 (2018). https://doi.org/10.1038/sdata.2018.185)
The Multi-Institutional Research in Alzheimer’s Genetic Epidemiology (MIRAGE) Study is a family study funded by the NIA that began in 1991. The goal of MIRAGE is to identify genetic and non-genetic risk factors for Alzheimer’s disease. Approximately 2,500 members of 1,000 Caucasian and African American families were recruited and blood was collected for DNA and cell lines. These families included both subjects who are cognitively normal and others meeting NINCDS/ADRDA criteria for probable or definite AD. Subjects were ascertained at 17 centers in the US, Canada, Germany and Greece.
The National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) family cohort was started in 1990 and consists of families with two or more members with early or late onset AD and related dementias. This collection maintains DNA and cell lines on affected family members and unaffected relatives (typically over age 60). These families are not evaluated in person and all clinical information is obtained through medical record review. Therefore, data is limited to the following: family history; demographic data; medical records on the evaluation; diagnosis and treatment of symptomatic subjects; telephone cognitive battery; neuropathological findings when available. This is a longitudinal study with autopsy available to all participants. Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs), and PBMCs are available. Fixed and/or frozen brain tissue is available on all individuals as well.
Case studies generated for members of this cohort include clinical data regarding onset and progression of cognitive problems, medical history and medications, family history of memory problems, neurological history and examination results, psychiatric history and examination results, neuropsychological examination results, and diagnostic imaging and laboratory results. In addition to demographic data, a clinical history, and a neurological history and examination, virtually all of the case summaries included a computed tomographic or magnetic resonance imaging scan, laboratory studies, at least a brief description of behavioral symptoms and/or signs, and a Mini-Mental State Examination and/or more detailed neuropsychological testing.
Diagnosticians followed the NINCDS-ADRDA criteria for the diagnosis of probable and possible AD, with two further specifications. First, a gradual progressive language deficit as the initial symptom would warrant a diagnosis of possible, not probable, AD. This change was instituted based on recent autopsy findings that such patients sometimes do not have AD. Second, subjects with a prominent early behavioral disturbance should have a diagnosis of possible AD based on evidence that such patients do not invariably have AD.
In phase 1 of the study, at least two clinicians at each of the two non-originating sites rated each patient as having probable AD, possible AD, or non-AD using the modified NINCDS-ADRDA criteria described above. All diagnosticians were “blinded” to the autopsy diagnosis and were not told which of the other two sites had provided the case. Where internal disagreements occurred, the clinicians at each site discussed the cases informally and agreed on a clinical diagnosis, which was tabulated as a pre-consensus diagnosis. In phase 2 of the study, consensus conferences were conducted for each case on which the non-originating sites disagreed, and post-consensus diagnoses (including the cases with agreement) were tabulated.
The LOAD collection is a longitudinal, multi-center late onset AD sibling genetics initiative. This NIA-funded study began in 2002 and maintains DNA and cell lines on families with 2 or more siblings with AD (at least one probable or confirmed AD) (n=5291). A third family member who is either affected or unaffected is also required. These individuals are evaluated in person and/or over the phone. A minimum dataset is collected for each person in the family. Definite AD is defined by established neuropathological criteria (and confirmed by autopsy). Probable or possible AD is defined according to NINCDS-ADRDA criteria. Autopsy is offered to all subjects.
The NIA ADRC cohort included subjects ascertained and evaluated by the clinical and neuropathology cores of the 32 NIA-funded ADRCs. Data collection is coordinated by the National Alzheimer’s Coordinating Center (NACC). NACC coordinates collection of phenotype data from the 32 ADRCs, cleans all data, coordinates implementation of definitions of AD cases and controls, and coordinates collection of samples. The ADRC cohort consists of autopsy-confirmed and clinically-confirmed AD cases, and cognitively normal elders (CNEs) with complete neuropathology data who were older than 60 years at age of death, and living CNEs evaluated using the Uniform dataset (UDS) protocol who were documented to not have mild cognitive impairment (MCI) and were between 60 and 100 years of age at assessment.
Based on the data collected by NACC, the ADGC Neuropathology Core Leaders Subcommittee derived inclusion and exclusion criteria for AD and control samples. All autopsied subjects were age ≥ 60 years at death. AD cases were demented according to DSM-IV criteria or Clinical Dementia Rating (CDR) ≥1. Neuropathologic stratification of cases followed NIA/Reagan criteria explicitly, or used a similar approach when NIA/Reagan criteria were coded as not done, missing, or unknown. Cases were intermediate or high likelihood by NIA/Reagan criteria with moderate to frequent amyloid plaques and neurofibrillary tangle (NFT) Braak stage of III-VI. Persons with Down syndrome, non-AD tauopathies and synucleinopathies were excluded. All autopsied controls had a clinical evaluation within two years of death.
Controls did not meet DSM-IV criteria for dementia, did not have a diagnosis of mild cognitive impairment (MCI), and had a CDR of 0, if performed. Controls did not meet or were low-likelihood AD by NIA/Reagan criteria, had sparse or no amyloid plaques, and a Braak NFT stage of 0 – II. ADRCs sent frozen tissue from autopsied subjects and DNA samples from some autopsied subjects and from living subjects to the ADRCs to the National Cell Repository for Alzheimer’s Disease (NCRAD). DNA was prepared by NCRAD for genotyping and sent to the genotyping site at Children’s Hospital of Philadelphia. ADRC samples were genotyped and analyzed in separate batches.
The Northern Manhattan Study (NOMAS) is a research study of stroke and stroke risk factors among the multi-ethnic community of Northern Manhattan, New York.
The study is a collaboration between the Department of Neurology at University of Miami and the Neurological Institute at Columbia University.
NOMAS is a NINDS-funded study of the population of Washington Heights in Northern Manhattan. The ongoing study, which began in 1990, is now a collaboration between the Department of Neurology at University of Miami and the Neurological Institute at Columbia University. The study’s interdisciplinary team of doctors and researchers has enrolled over 4,400 people from the community, some of whom have suffered a stroke or related neurological diseases (Sacco et al. 2004).
The Peru Alzheimer’s Disease Initiative (PeADI) is being conducted at several sites in Peru including Lima (Marca-Ysabel et al. 2021). The Mestizo population living in Lima, the capital city, is comprised of ~76% of Amerindian, 11% Southern European, and 3% Northern African ancestries, and a smaller proportion of western central Africa, western central Europe, Finland, northern Siberia and Jewish diaspora. Cases will be clinic based and controls will be clinic and community based.
Participants were ascertained for an AD/ADRD Memory Study, including healthy controls. Eligibility was based on self-reported Peruvian heritage with mestizo and Quechua being the two most frequent self-descriptors. This cohort is an admixed Hispanic/Latino population with substantial Amerindian descent. Most participants were recruited in Lima and surrounding areas to the north (e.g., Huacho).
Participants were ascertained and evaluated through local memory clinics (Instituto Nacional de Ciencias Neurologicas – INCN) and community centers. Some participants were evaluated in their homes. All participants greater than 65 years of age underwent a screening and standard clinical evaluation consisting of a medical and family history interview, neuropsychological testing, behavioral and emotional assessments, and functional measures. Venous blood samples (or saliva samples when needed) were collected on all participants. All assessments were conducted in the preferred language of the participant or knowledgeable informant.
Description coming soon.
Patients with a clinical Parkinsonism in life and neuropathological confirmation of Progressive Supranuclear Palsy (PSP) were identified from brain banks, research hospitals and neuropathologists. The top three contributing sites were the Mayo Clinic, Harvard Brain Tissue Resource Center at McClean Hospital, and the University of Pennsylvania and additional small numbers of cases were obtained from various other institutions across the US. The neuropathological diagnosis was made according to NINDS neuropathologic diagnostic criteria. DNA was extracted from brain tissue from patients who had consented for brain donation. DNA samples and/or tissue were sent to the University of Pennsylvania for preparation for genotyping.
This study includes subjects with Progressive Supranuclear Palsy (PSP). Subjects were enrolled in the davenutide PSP Phase Trail 2/3. Additional subjects were clinically diagnosed PSP at the University of California, San Francisco Memory and Aging Center.
Participants met the modified Neuroprotection and Natural History in Parkinson Plus Syndrome study criteria for PSP.
See https://clinicaltrials.gov/ct2/show/NCT01110720 for comprehensive inclusion and exclusion criteria.
Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014;13(7):676-685. doi:10.1016/S1474-4422(14)70088-2. PMID: 24873720
The Puerto Rican 10/66 Study (PR1066) (https://www.alz.co.uk/1066/), is an Alzheimer’s Disease International study of dementia in Puerto Rico that began in 2007 (Dr. Ivonne Jimenez-Velazquez, PI). Individuals were recruited as part of the the 10/66 Population Based Study of Dementia using standard protocols. As part of this study, sociodemographic information and detailed clinical history of memory decline were collected. In addition, the Clinical Dementia Rating scale (CDR), and Community Screening Interview for Dementia, and Petersen ADL criteria were collected for all individuals. Neurocognitive testing (CERAD battery) was available for some participants. Participants were adjudicated for dementia. Lastly, the total number of samples that were whole genome sequenced is 1,565 with the breakdown of 140 Cases; 1,245 Controls and 180 MCI’s.
Prince M, Ferri CP, Acosta D, et al. The protocols for the 10/66 dementia research group population- based research programme. BMC Public Health. 2007;7(1):165.
The Puerto Rican Alzheimer’s Disease Initiative (PRADI) is a NIH NIA study of late-onset Alzheimer disease focused on the Caribbean-Hispanic Puerto Rican population. Participants were ascertained for an AD/ADRD Memory Study, including healthy controls. Eligibility was based on self-reported Puerto Rican heritage. Most participants were recruited in the Island of Puerto Rico with a small fraction being ascertained in South Florida, New York, and Connecticut.
Participants were ascertained and evaluated through community centers, private memory clinics and adult day care centers. Some participants were evaluated in their homes. All participants greater than 60 years of age underwent a standard clinical evaluation consisting of a medical and family history interview, neuropsychological testing, behavioral and emotional assessments, and functional measures. Venous blood samples (or saliva samples when needed) were collected on all participants. All assessments were conducted in the preferred language of the participant or knowledgeable informant.
The Religious Orders Study (ROS) is a longitudinal, epidemiologic clinical-pathological study of memory, motor, and functional problems in older Catholic nuns, priests, and brothers aged 65 years and older from across the United States. Participants without known dementia agree to medical and psychological evaluation each year and brain donation after death. Since 1994, approximately 1,200 older persons have been enrolled and 580 are currently alive. Participants also have yearly blood draws which result in the storage of serum, plasma and cells.
The Memory and Aging Project (MAP) is a longitudinal, epidemiologic clinical-pathologic study of dementia and other chronic diseases of aging. Older persons are recruited from about 40 continuous care retirement communities and senior subsidized housing facilities around the Chicago metropolitan area. Participants without known dementia agree to annual detailed clinical evaluation and donation of brain, spinal cord and muscle after death. MAP began in 1997 and over 1,600 older adults have enrolled. Approximately 1,000 participants are currently alive. Participants also have yearly blood draws which result in the storage of serum, plasma and cells.
Clinical evaluation, self-report, and medication inspection are used to document medical conditions. The diagnostic process is the same for ROS and MAP. Briefly, a decision tree designed to mimic expert clinical judgment was implemented by computer to inform several clinical diagnoses, including dementia and AD. It combines data reduction techniques for the cognitive performance testing with a series of discrete clinical judgments made in series by a neuropsychologist and a clinician. Presumptive diagnoses of dementia and AD are calculated that conform to accepted clinical criteria. The clinician is asked to agree or disagree with the decisions. An algorithm uses these decisions to provide diagnoses of MCI and amnestic MCI. Persons with MCI are judged to have cognitive impairment by neuropsychologic testing without a diagnosis of dementia by the clinician. Persons without dementia or MCI are categorized as having no cognitive impairment (NCI).
Subjects are also evaluated neurologically every year, and, at the time of death, a review of all ante-mortem data leads to a final clinical diagnosis for each participant: each individual receives a diagnosis of syndromic Alzheimer’s disease (AD), of mild cognitive impairment (MCI), or of no cognitive impairment (NCI). After the autopsy is concluded, a spectrum of neuropathologic diagnoses are obtained, such as a pathologic diagnosis of AD as defined using the modified NIA Reagan criteria based on a modified Bielschowsky silver stain to visualize amyloid plaques and neurofibrillary tangles.
The Research in African-American Alzheimer’s Disease Initiative (REAAADI) is a NIH NIA study focused on identifying genetic factors for Alzheimer disease within the African-American population in order to detect new targets for drug development and improve accessibility to Alzheimer’s disease education within the community. Participants were ascertained for multiple studies of AD/ADRD over the past 20 years, including healthy controls. Eligibility across studies was based on self-reported African American heritage. While participants were enrolled initially as part of larger studies of AD/ADRD, the first formal study focusing exclusively on African Americans began in in 2007 (Genetic Epidemiology of Alzheimer’s Disease in African Americans; AG028786). Ascertainment has continued since 2007 as part of multiple studies of AD/ADRD including the REAAADI Study (AG052410). Since 2007, participants have been ascertained via academic centers in North Carolina (Duke University, NC &T, Wake Forest University), Florida (University of Miami), New York (Columbia University), Ohio (Case Western University) and Tennessee (Vanderbilt University).
Participants were ascertained and evaluated through community centers, private memory clinics and adult day care centers. Some participants were evaluated in their homes. All participants greater than 60 years of age underwent a standard clinical evaluation consisting of a medical and family history interview, neuropsychological testing, behavioral and emotional assessments, and functional measures. Venous blood samples (or saliva samples when needed) were collected on all participants. All assessments were conducted in the preferred language of the participant or knowledgeable informant. Note that the assessment protocols have changed over the years, but a core group of clinical measures (including neuropsychological tests) are available for all participants.
The Rotterdam Elderly Study is a prospective cohort study in the Ommoord district in the city of Rotterdam, the Netherlands [Hofman et al., 1991]. Following the pilot in 1989, recruitment started in January 1990. The main objectives of the Rotterdam Study were to investigate the risk factors of cardiovascular, neurological, ophthalmological and endocrine diseases in the elderly. Up to 2008, approximately 15,000 subjects aged 45 years or over have been recruited. Participants were interviewed at home and went through an extensive set of examinations, bone mineral densitometry, including sample collections for in-depth molecular and genetic analyses. Examinations were repeated every 3-4 years in potentially changing characteristics. Participants were followed for the most common diseases in the elderly, including coronary heart disease, heart failure and stroke, Parkinson’s disease, Alzheimer’s disease and other dementias, depression and anxiety disorders, macular degeneration and glaucoma, diabetes mellitus and osteoporosis.
In the baseline and follow-up examinations participants undergo an initial screen for dementia with the Mini Mental State Examination (MMSE) and the Geriatric Mental Schedule (GMS), followed by an examination and informant interview with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) in screen positives (MMSE <26 or GMS >0), and subsequent neurological, neuropsychological and neuroimaging examinations. Of subjects who cannot be reexamined in person, information is obtained from the GPs and the regional institute for outpatient mental health care. A consensus panel makes the final diagnoses in accordance with standard criteria (DSM-III-R criteria; NINCDS-ADRDA; NINDS-AIREN).
This cohort contains samples from Brains for Dementia Research (BDR) Genetics project (Dr. Kevin Morgan, PI and Directory of the Alzheimer’s Research UK (ARUK) DNA Consortium and BDR).
The BDR cohort and program was for planned brain donation across five UK brain banks and one donation point, with standardized operating procedures, following longitudinal clinical and psychometric assessments for people with no cognitive impairment as well as those with dementia. See the Francis et al. publication for a detailed description about the BDR cohort set-up, clinical data, and psychometric assessment measures collected.
Francis PT, Costello H, Hayes GM. Brains for Dementia Research: Evolution in a Longitudinal Brain Donation Cohort to Maximize Current and Future Value. J Alzheimers Dis. 2018;66(4):1635-1644. doi:10.3233/JAD-180699
Data from the Texas Alzheimer’s Research and Care Consortium (TARCC) includes cases enrolled at several major medical research institutions (as of 2013 this included Baylor College of Medicine, Texas Tech University Health Sciences Center, University of North Texas Health Science Center, The University of Texas Health Sciences Center at San Antonio, The University of Texas Southwestern Medical Center, and Texas A & M Health Science Center).
Individuals must be at least 55 years of age with a diagnosis of probable AD or normal cognition based on a Clinical Dementia Rating Global Score of 0. Clinical, neurological, and neuropsychological examinations performed at each site follow the TARCC research protocol that has been adopted from the standard clinical work-up for dementia. All subjects are examined at baseline and at each annual follow-up visit.
Information is obtained from the clinical and neurological examination on age at onset of symptoms (if AD patient), family history of dementia in first degree relatives, cardiovascular disease and cardiovascular disease risk factors. Subjects also undergo a battery of neuropsychological tests as part of the TARC research protocol, with all information reviewed by a consensus panel made up of at least a physician, neuropsychologist, and research coordinator at each site to assign the final clinical diagnosis according to NINCDS-ADRDA criteria.
Each affected individual met NINCDS-ADRDA criteria for probable or definite AD with age at onset greater than 60 years, as determined from specific probe questions within the clinical history provided by a reliable family informant or from documentation of significant cognitive impairment in the medical record. Cognitively healthy controls were unrelated individuals from the same catchment areas and frequency matched by age and gender, and had a documented MMSE or 3MS score in the normal range.
Samples sequenced in ADSP-FUS1 include participants from the John P. Hussman Institute for Human Genomics (HIHG) Brain Bank. The HIHG Brain, Bank autopsy individuals followed the typical clinical course of disease. This sample is a clinic and community outreach sample ascertained in North and South Carolina and Virginia.
The University of Miami Brain Bank Cohort was ascertained through self-referred cases and controls to the University of Miami Brain Endowment Bank, a National Institutes of Health (NIH) NeuroBioBank, one of six designated brain and tissue biorepositories in the nation. Medical records are available on all cases and controls, all of whom were tested before death for cognitive function.
Subjects included in the University of Miami Brain Endowment Bank cohort include individuals who were donors to the University of Miami Brain Endowment Bank from 1986 to 2020. Donors were either individuals with history of cognitive impairment and neuropathological changes consistent with Alzheimer disease, or cognitively unaffected individuals without such neuropathological changes. Participants were recruited from community organizations, organ/tissue donation program registries, or self-referral. This is an autopsy-based study designed to analyze post-mortem brain tissue. Medical records are also obtained as available to help correlate brain behavior relationships.
Study participants were enrolled at the University of Pittsburgh Alzheimer’s Disease Research Center (ADRC), all of whom met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association clinical criteria for probable AD. Each participant had undergone an extensive neuropsychiatric evaluation, which has been described in detail previously. Briefly, this involved a physical examination, neurological examination, semistructured psychiatric interview, and neuropsychological assessment. All patient records were reviewed at a multidisciplinary clinical consensus conference for assignment of a diagnosis. The inclusion/exclusion criteria have been published previously, but it is important to note that one of the criteria was that all the patients had to have a reliable caregiver that could provide detailed information about the patients’ clinical symptoms and their activities of daily living (ADLs). The caregiver was interviewed in person once a year and by phone every 6 months. In case of loss of a caregiver, the data were censored as the last date that reliable information was received from the caregiver.
Lopez OL, Becker JT, Saxton J, Sweet RA, Klunk W, DeKosky ST. Alteration of a clinically meaningful outcome in the natural history of Alzheimer’s disease by cholinesterase inhibition. J Am Geriatr Soc. 2005 Jan;53(1):83-7. doi: 10.1111/j.1532-5415.2005.53015.x. PMID: 15667381.
This study was carried out under the direction of Dr. Peter St George-Hyslop and Dr Rogaeva at the Tanz Centre for Research in Neurodegenerative Diseases (CRND), University of Toronto. In order to explore the potential role of hereditary factors, a registry at the Tanz CRND with a coordinator was established for families in which two or more individuals have the suspected diagnosis of Alzheimer’s Disease or other forms of dementia. Eligibility requirements were disseminated through the CRND website. Individuals who contacted the Registry received a family history questionnaire in the mail. For sufficiently informative families, researchers sought consent to obtain blood samples from available family members required for genetic research. Collaborating neurologists and genetic counselors also referred families that fit the requirements. All collected individuals were given numeric IDs to protect their privacy. Families were eligible if: two or more members, living or decease, were affected by Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis, frontal temporal dementia or Creutzfeldt-Jacob Disease. Families were ineligible if: there were fewer than 2 affected members or family history was unavailable to document.
131 families with LOAD (751 individuals) were ascertained and evaluated through the University of Washington Alzheimer Disease Research Center. Clinical and neuropathological assessments of cases and controls, including blood sampling, medical record reviews, brain autopsies, and genetic analyses were performed under protocols approved by the institutional review boards of the University of Washington and the Seattle Veterans Affairs Puget Sound Health Care System.
The UM/VU dataset contains 1,186 cases and 1,135 CNEs (new and previously published) ascertained at the University of Miami and Vanderbilt University, including 409 autopsy-confirmed cases and 136 controls. An additional 16 cases were included and 34 controls excluded from the data analyzed in the prior study. Each affected individual met NINCDS-ADRDA criteria for probably or definite AD with age at onset greater than 60 years as determined from specific probe questions within the clinical history provided by a reliable family informant or from documentation of significant cognitive impairment in the medical record. Cognitively healthy controls were unrelated individuals from the same catchment areas and frequency matched by age and gender, and had a documented MMSE or 3MS score in the normal range. Cases and controls had similar demographics: both had ages-at-onset/ages-at-exam of 74 (± 8 standard deviations), and cases were 63% female, and controls were 61% female.
Since inception of the study in 1992, over 6,000 participants have enrolled in the Washington Heights and Inwood Community Aging project (WHICAP). The cohort participants were nondemented initially, 65 years of age or older, and comprised of non‐Hispanic whites (32%), African Americans (28%), and Caribbean Hispanics from the Dominican Republic (44%). During each assessment, participants received a neuropsychological test battery, medical interview, and were re‐consented for sharing of genetic information and autopsy. A consensus diagnosis was derived for each participant by experienced clinicians based on NINCDS‐ADRDA criteria for possible, probable, or definite AD, or moderate or high likelihood of neuropathological criteria of AD. Every individual with whole‐exome sequencing has at least a baseline and one follow‐up assessment and examination, and for those who have died, the presence or absence of dementia was determined using a brief, validated telephone interview with participant informants: The Dementia Questionnaire (DQ) and the Telephone Interview of Cognitive Status (TICS).
Over the length of the project, WHICAP have identified environmental, health-related and genetic risk factors of disease and predictors of disease progression by collecting longitudinal data on cognitive performance, emotional health, independence in daily activities, blood pressure, anthropometric measures, cardiovascular status and selected biomarkers in this elderly, multi-ethnic cohort. Biomarker studies include lipids, amyloid peptides, sex hormones, homocysteine, insulin and C-reactive protein (CRP), and MRI in these elderly participants. WHICAP have reported that the rates of disease and the frequency of disease risk factors vary across ethnic groups, and have identified one of the largest, multi-ethnic groups of incident LOAD cases.
The Wisconsin Registry for Alzheimer’s Prevention (WRAP) is an ongoing longitudinal observational cohort study of individuals age 40-65 at baseline who do not have dementia. Since 2001, WRAP has enrolled more than 1,700 individuals, 73% of whom had a parental history of probable Alzheimer’s disease (AD) dementia. Participants return for a second visit approximately 4 years after baseline, and subsequent visits occur every 2 years. At each visit, a cognitive test battery is administered, self-reported medical and lifestyle histories (e.g., diet, physical and cognitive activity, sleep, and mood) are assessed via questionnaire, and blood is drawn for laboratory tests, metabolomics, and genomics. A subset of participants have also undergone molecular imaging, structural imaging, and cerebrospinal fluid collection for biomarker measurement.
GeneRations Of WRAP (GROW) is an ancillary study to the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study enriched for individuals with a parental history of probable Alzheimer’s disease (AD) dementia. GROW is a family study that recruited extended family members of existing WRAP participants. Genomic data from family members with probable AD dementia were collected via banked brains or saliva. Individuals free of dementia and within the WRAP eligibility age of 40-65 were enrolled in WRAP. At each study visit, a cognitive test battery is administered, self-reported medical and lifestyle histories (e.g., diet, physical and cognitive activity, sleep, and mood) are assessed via questionnaire, and blood is drawn for laboratory tests, metabolomics, and genomics. A subset of participants have also undergone molecular imaging, structural imaging, and cerebrospinal fluid collection for biomarker measurement.