Study Design

The first wave of LASI-DAD drew a sub-sample of respondents from the baseline LASI sample aged 60 and older from 18 states and union territories. A two-stage stratified random sampling approach was adopted, oversampling individuals at high risk of cognitive impairment to ensure enough respondents with dementia or mild cognitive impairment. To accomplish this, we first classified respondents into those at high and low risk of cognitive impairment based on the core LASI study’s cognitive tests and on the proxy report for those who did not complete the cognitive tests. Specifically, we grouped the LASI respondents by age (60–69 and 70+) and education (no formal schooling vs. any education) and, within these groups, by relative performance on a battery of cognitive tests and proxy interviews.

In Wave 2, we followed the same sampling procedure. However, we also recruited newly age-qualifying older adults ages 60-64 and refresher sample of those ages 65 and older, as we expected higher mortality rates due to the COVID-19 pandemic. The sample was also expanded from 18 to 22 states and union territories, improving the population representativeness.

The first wave of LASI-DAD drew a sub-sample of respondents from the baseline LASI sample aged 60 and older from 18 states and union territories. Wave 1 was fielded in three phases from 2017 to 2019. A two-stage stratified random sampling approach was adopted, oversampling individuals at high risk of cognitive impairment to ensure enough respondents with dementia or mild cognitive impairment. To accomplish this, we first classified respondents into those at high and low risk of cognitive impairment based on the core LASI study’s cognitive tests and on the proxy report for those who did not complete the cognitive tests. Specifically, we grouped the LASI respondents by age (60–69 and 70+) and education (no formal schooling vs. any education) and, within these groups, by relative performance on a battery of cognitive tests and proxy interviews.

Wave 2 was also fielded in three phases from 2022 – 2024. In Wave 2, we followed the same sampling procedure. However, we also recruited newly age-qualifying older adults ages 60-64 and refresher sample of those ages 65 and older, as we expected higher mortality rates due to the COVID-19 pandemic. The sample was also expanded from 18 to 22 states and union territories, improving the population representativeness.

We administer the following list of cognitive tests:

  1. Literacy Test*
  2. Hindi Mental State Exam1
  3. HRS Orientation2
  4. Word Recall (Learning)3
  5. Word Recall (Delayed)3
  6. Word List Recognition3
  7. Digit Span Forward and Backward4
  8. Symbol Cancellation5
  9. Logical Memory4
  10. Logical Memory (Delayed)4
  11. Logical Memory (Recognition)4
  12. Constructional Praxis6
  13. Constructional Praxis (Recall)6
  14. Retrieval Fluency7
  15. Judgement & Problem Solving8
  16. Serial 7s9
  17. Raven’s Standard Progressive Matrices10
  18. Community Screening Interview for Dementia (CSI-D11)
  19. Go-NoGo Test12
  20. Trail Making Test*13.14
  21. Hand Movement Sequencing Test15
  22. Token Test16
*New in Wave 2

Resources

  1. Ganguli M, Ratcliff G, Chandra V, et al. A Hindi Version of the MMSE: The Development of a Cognitive Screening Instrument for a Largely Illiterate Rural Elderly Population in India. Int J of Geriatric Psychiatry. 1995;10(5): 367–77. https://doi.org/10.1002/gps.930100505.
  2. Brandt J, Spencer M, Folstein, M. The Telephone Interview for Cognitive Status. Neuropsychiatry, Neuropsychol. Behav. Neurol. 1988;1(2): 111–1
  3. CERAD. 1987. Consortium to Establish a Registry for Alzheimer’s Disease: Clinical Assessment Packet for Clinical/Neuropsychological Assessment for Alzheimer’s Disease. https://sites.duke.edu/centerforaging/cerad/.
  4. Wechsler D. 2009. Wechsler Memory Scales—Fourth Edition (WMS-IV): Technical and Interpretive Manual. San Antonio, Texas: Pearson Clinical Assessment. https://www.pearsonassessments.com/store/usassessments/en/Store/Professional-Assessments/Cognition-%26-Neuro/Wechsler-Memory-Scale-%7C-Fourth-Edition/p/100000281.html.
  5. Lowery N, Ragland JD, Gur RC, Gur RE, Moberg PJ. Normative data for the symbol cancellation test in young healthy adults. Appl Neuropsychol. 2004;11(4):218-221. doi:10.1207/s15324826an1104_8
  6. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. AmJ Psychiatry. 1984;141(11):1356-1364. doi:10.1176/ajp.141.11.1356
  7. Woodcock RW, McGrew KS, Mather N. The Woodcock–Johnson III (WJIII), Tests of Achievement. Itasca, IL: Riverside Publishing Co. 2001
  8. Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43(11):2412–4.
  9. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-198. doi:10.1016/0022-3956(75)90026-6
  10. Raven J. The Raven's progressive matrices: change and stability over culture and time. Cogn Psychol. 2000;41(1):1-48. doi:10.1006/cogp.1999.0735
  11. Hall KS, Hendrie HC, Brittain HM. The Development of a Dementia Screening Interview in 2 Distinct Languages. Int J Meth Psych Res. 1993;3(1):1–28.
  12. Gomez P, Ratcliff R, Perea M. A model of the go/no-go task. J Exp Psychol Gen. 2007;136(3):389-413. doi:10.1037/0096-3445.136.3.389
  13. Humphreys, G. W., Duta, M. D., Montana, L., Demeyere, N., McCrory, C., Rohr, J., Kahn, K., Tollman, S., & Berkman, L. (2017). Cognitive Function in Low-Income and Low-Literacy Settings: Validation of the Tablet-Based Oxford Cognitive Screen in the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). The journals of gerontology. Series B, Psychological sciences and social sciences, 72(1), 38–50. https://doi.org/10.1093/geronb/gbw139
  14. Farrell, M. T., Kobayashi, L. C., Montana, L., Wagner, R. G., Demeyere, N., & Berkman, L. (2020). Disparity in Educational Attainment Partially Explains Cognitive Gender Differences in Older Rural South Africans. The journals of gerontology. Series B, Psychological sciences and social sciences, 75(7), e161–e173. https://doi.org/10.1093/geronb/gbaa035
  15. Mattis S. Dementia Rating Scale. Professional Manual. Florida: Psychological Assessment Resources. 1988.
  16. De Renzi E, Vignolo LA. The token test: A sensitive test to detect receptive disturbances in aphasics. Brain. 1962;85:665-678. doi:10.1093/brain/85.4.665

The informant is someone who knows the respondent well, interacts with them frequently, and therefore knows their ability to complete daily functions and can report on them. Informants are most likely to be spouses, partners, children, or caregivers. Occasionally, they may be other relatives, friends, or neighbors.

The informant report includes:

  1. Demographics: asks about the informant's demographic characteristics and relationship with the respondent
  2. JORM IQCODE:1 asks about changes they observed about the respondent's cognitive abilities and memory compared to 10 years ago
  3. Blessed Scale Part 2:2 asks questions about the respondent's ability to take care of themselves without assistance or with some level of assistance
  4. Activities: asks about activities the respondent is doing, the frequency with which they are doing these activities, and whether they are doing them alone or with someone else
  5. Affect: asks about the feelings the respondent experienced during their day while doing various activities
  6. CSI-D (Community Screening Instrument – Dementia):3 asks about the level of decline the respondent experienced while doing various daily activities in the past few years
  7. Blessed Scale Part 1:2 asks about the respondent's loss of ability
  8. Judgement and Problem Solving*:asks about the respondent’s social behavior, disinhibition, and their ability to handle emergencies
  9. Caregiver Stress and Burden*4-7:assesses caregiver’s stress, depression, psychological overload, and positive attributes of caregiving
*New in Wave 2

Resources

  1. Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med. 1989;19(4):1015-1022. doi:10.1017/s0033291700005742
  2. Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968;114(512):797-811. doi:10.1192/bjp.114.512.797
  3. Hall KS, Hendrie HC, Brittain HM. The Development of a Dementia Screening Interview in 2 Distinct Languages. Int J Meth Psych Res. 1993;3(1): 1–28.
  4. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385-396.
  5. Radloff L. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.
  6. Bédard M, Molloy DW, Squire L, Dubois S, Lever JA, O'Donnell M. The Zarit Burden Interview: a new short version and screening version. Gerontologist. 2001;41(5):652-657. doi:10.1093/geront/41.5.652
  7. Given CW, Given B, Stommel M, Collins C, King S, Franklin S. The caregiver reaction assessment (CRA) for caregivers to persons with chronic physical and mental impairments. Res Nurs Health. 1992;15(4):271-283. doi:10.1002/nur.4770150406

We assess the respondent's physical, mental, and functional health. Our geriatric assessment includes:

  1. Anthropometry: height, weight, mid-arm circumference, calf circumference, head circumference*, waist circumference*
  2. Blood pressure and pulse: systolic and diastolic blood pressure measurements and pulse measurements were taken.
  3. Functional health1,2: activities of daily living, instrumental activities of daily living, mobility*, fall risk*
  4. Timed up and go test**,3: A test for quantifying functional mobility for frail elderly persons
  5. Mental health4,5: Center for Epidemiological Studies - Depression, Beck's Anxiety Inventory
  6. 6-Minute walk test**,6: A test for functional capacity measuring the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.
  7. Chair stands*: A repeated chair stand test was added to assess lower- extremity function.
  8. Mini Nutritional Assessment7: Rapid assessment of nutritional status in older adults.
  9. Audiometry Test*,8: A pure-tone audiometry test was administered, using the hearTest from the hearX group on a tablet.
  10. Venous blood collection: Certified and trained phlebotomists drew 17 mL of VBS from respondents. Whole blood and serum- based assays were conducted.
*New in Wave 2**Wave 1 only

Resources

  1. Mahoney, F. I., and D. W. Barthel. 1965. Functional evaluation: The barthel index: A simple index of Independence useful in scoring improvement in the rehabilitation of the chronically Ill. Maryland State Medical Journal 14:61–65.
  2. Lawton, M. P., and E. M. Brody. 1969. Assessment of older people: Self-maintaining and instrumental activities of daily living. The Gerontologist 9(3_Part_1:179–86. doi:10.1093/geront/9.3_Part_1.179.
  3. Podsiadlo D, Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142-148. doi:10.1111/j.1532-5415.1991.tb01616.x
  4. Radloff L. The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.
  5. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56(6):893-897. doi:10.1037//0022-006x.56.6.893
  6. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111–7.
  7. Vellas B, Guigoz Y, Garry PJ, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition. 1999;15(2):116-122. doi:10.1016/s0899-9007(98)00171-3
  8. hearTest by hearX Group - Pure tone clinical audiometer. Available at https://www.hearxgroup.com/heartest. Accessed: August 5th, 2024.

We have obtained brain images from a subsample of LASI-DAD respondents, using magnetic resonance imaging (MRI).

We acquired a 40-45 minute high-resolution 3T protocol, following the Alzheimer's Disease Neuroimaging Initiative (ADNI) protocol. Our MRI protocol consists of T1w, T2w, FLAIR, SWI, multi-shell DWI and resting state fMRI sequences. Scan sequences such as T1w, T2w, DWI, FLAIR and SWI allow us to measure structural properties of the brain that are associated with healthy aging, MCI and dementia, while resting state fMRI can be used to help decipher functional differences that develop as individuals begin to lose cognitive functionality.

Structural and functional images can be compared with the other areas of our study, including genetics, cognitive and behavioral testing, and blood biomarkers. Such analysis offers an opportunity to study how structural and functional MRI aligns with behavioral and cognitive deficits.

Neuroimaging data for a subsample of Wave 1 respondents (N=137) are available through the Image and Data Archive (IDA) online database hosted by the Laboratory of Neuro Imaging (IDA) at the University of Southern California. All available MRI modalities are available to download in DICOM or NIFTI formats. Permission can be requested by signing and submitting a data use application.

Neuroimaging Partner Institutions

Medical College KolkataInstitute of Neurosciences, Kolkata (INK)
  • Dr. Soumik Das
  • Dr. Arunansu Talukdar
Sanjivini Scanning Solutions, Chandigarh
  • Dr. Niranjan Khandelwal
NIMS University Jaipur, Rajasthan
  • Dr. Niranjan Khandelwal
Narula Diagnostics, Gurugram, Delhi/Haryana
  • Dr. Niranjan Khandelwal
  • Dr. Arjun Narula
AIIMS Mangalagiri, Andhra Pradesh
  • Dr. Prudhvinath Reddy
NM Medical Center Mumbai
  • Rahil Shah
NIMHANS, Bangalore
  • Manisha Devi
  • Dr. PT Sivakumar
  • Dr. Harshita Viswakarma
  • Dr. John John
Guwahati, Assam
  • Dr. Niranjan Khandelwal
  • Dr. Nirod Medhi
Graphic Era Institute of Medical Sciences at Dehradun
  • Dr. Jyoti Dangwal
  • Dr. Sudhir Saxena

Overview

Genomics has been one of the key initiatives of the LASI-DAD study. As the first step under this initiative, we conducted the whole genome sequencing (WGS) validation study on a small number of samples. This study demonstrated the feasibility of collecting blood samples in the field that could be shipped effectively to our industry partner and from which we could obtain high-quality genotyping measures. We then genotyped 960 geographically dispersed LASI-DAD respondents, using the Illumina Infinium Global Screening Array-24 v2.0 (GSA) BeadChip. It contains over 640,000 genetic markers including highly optimized multi-ethnic genome-wide content, curated clinical research variants, and QC markers.

Polygenic Risk Scores

Since health outcomes and traits are often highly polygenic, reflecting the aggregate effect of many different genes, the use of single variants or candidate genes may not capture the dynamic nature of more complex phenotypes. In light of this, polygenic risk scores (PRS) were constructed for Alzheimer’s Disease and general cognitive functioning for consenting LASI-DAD respondents who provided whole blood DNA in 2018. These scores will help harmonize research across studies conducted by LASI-DAD data users.

Global Screening Array

Data are available for download through The National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) and includes the following:

  • GWAS Data: Original genotype data from the GSA array, containing 1008 scans derived from 993 unique subjects (including 960 LASI-DAD subjects from the 100 Genomes Project)
  • 1000 G Imputed Data: Genotype data imputed to the 1000G reference panel (phase 3 v5)
  • TopMed Imputed Data: Genotype data imputed to the TOPMed reference panel (r2)

Whole Genome Sequencing

The LASI-DAD study is a part of the Alzheimer’s Disease Sequencing Project (ADSP). Whole Genome Sequencing has been completed for 2,686 participants from 18 states and union territories of India. Data is available for download through The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) as part of the Alzheimer's Disease Sequencing Program Umbrella release 4.