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.

Wave 1 was fielded in three phases from 2017 to 2019. Wave 2 was also fielded in three phases from 2022 – 2024.

We administer the following list of cognitive tests:

  1. Literacy Test*
  2. Hindi Mental State Exam
  3. HRS Orientation
  4. Word Recall (Learning)
  5. Word Recall (Delayed)
  6. Word List Recognition
  7. Digit Span Forward and Backward
  8. Symbol Cancellation
  9. Logical Memory
  10. Logical Memory (Delayed)
  11. Logical Memory (Recognition)
  12. Constructional Praxis
  13. Constructional Praxis (Recall)
  14. Retrieval Fluency
  15. Judgement & Problem Solving
  16. Serial 7s
  17. Raven’s Standard Progressive Matrices
  18. Community Screening Interview for Dementia (CSI-D)
  19. Go-NoGo Test
  20. Trail Making Test*
  21. Hand Movement Sequencing Test
  22. Token Test
*New in Wave 2

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: asks about changes they observed about the respondent's cognitive abilities and memory compared to 10 years ago
  3. Blessed Scale Part 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): asks about the level of decline the respondent experienced while doing various daily activities in the past few years
  7. Blessed Scale Part 1: 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*: assesses caregiver’s stress, depression, psychological overload, and positive attributes of caregiving
*New in Wave 2

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
  3. Functional health: activities of daily living, instrumental activities of daily living, mobility*, fall risk*
  4. Timed up and go test**
  5. Mental health: Center for Epidemiological Studies - Depression, Beck's Anxiety Inventory
  6. 6-Minute walk test**
  7. Chair stands*
  8. Mini Nutritional Assessment
  9. Audiometry Test*
  10. Venous blood collection
*New in Wave 2 **Wave 1 only

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 T1, T2, DTI, and FLAIR allow us to better comprehend the presentation and physical development of MCI and dementia, while resting state fMRI can be used to help decipher functional differences that develop as these 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 data aligns with behavioral and cognitive deficits.

Neuroimaging Partner Institutions

Medical College Kolkata Institute 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

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.