Shanghai At Risk for Alzheimer's Disease: a Cohort Study (SHARAD)

The goal of this cohort study is to estimate the incidence of AD in the first-degree relatives of patients with AD. The main questions it aims to answer are:

• cognitive changes of subjects at high risk of AD as ageing;
• environmental and behavioral factors affecting AD incidence.

Study Overview

• Status: Recruiting
• Conditions: Neurocognitive Disorders; Neurodegenerative Diseases; Cognitive Impairment; Dementia; Alzheimer Disease

Detailed Description

This study is a prospective cohort study focusing on the first-degree relatives of patients with Alzheimer's disease (AD). Multiple methods including the neuropsychiatric assessment battery, magnetic resonance imaging (MRI) and fluid biomarkers (blood and urine) are used to estimate the longitudinal changes of the participants at high risk of AD. Besides, a structured questionnaire is designed to investigate how environmental, behavioral and other factors influence the incidence of AD. This study is of great significance in establishing novel guidelines for the prevention and treatment of dementia suitable for Chinese population, and for clinicians to predict the risk of AD in first-degree relatives.

• Study Type: Observational
• Enrollment (Anticipated): 3418

Contacts and Locations

• Study Contact: Name: Gang Wang, MD, PhD; Phone Number: 086-021-64370045; Email: wg11424@rjh.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Ran Tang, MD; Phone Number: 18221457023; Email: hellotangran@163.com
      • Principal Investigator: Wang Gang, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population is the first-degree, cognition-preserved relatives (including parents, children and siblings of the same father and mother) of patients with AD

Description

Inclusion Criteria:

1. the AD diagnostic criteria of probands meet the 2011 National Institute on Aging - Alzheimer's Association framework, and participants are the first-degree relatives (including parents, children and siblings of the same father and mother) of the proband;
2. not patients with dementia;
3. ≥ 50 years, males and females;
4. subjects have lived in Shanghai for more than 1 year and have no plan to move out of Shanghai within 5 years;
5. subjects are able to complete investigation, physical examination, imaging examination and biological specimen collection.

Exclusion criteria:

Individuals will be excluded if they have:

1. other diseases which could cause cognitive decline, e.g. cerebrovascular diseases, Creutzfeldt-Jakob disease and Parkinsons disease;
2. history of psychological disorders (according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition);
3. uncorrectable visual or auditory impairment that hampers the completion of related examination.
4. pre-menopausal women will also be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of cognitive impairment at 5 years	Number of participants who covert to AD or mild cognitive impairment (MCI) will be recorded to calculate the incidence.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mini-Mental State Examination (MMSE) at 5 years	MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity.	5 years
Change From Baseline in Montreal cognitive assessment-Basic (MoCA) at 5 years	MoCA is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity.	5 years
Change From Baseline in Boston naming test (BNT) at 5 years	MoCA is a screening instrument used to assess object naming function. The total score ranges from 0 to 30, with lower scores indicating greater disease severity.	5 years
Change From Baseline in the auditory verbal learning test (AVLT) at 5 years	AVLT is a screening instrument used to assess the function of memory. The score in long-term memory (N5) ranges from 0 to 12, with lower scores indicating greater disease severity.	5 years
Change From Baseline in trail making test (TMT) at 5 years	AVLT is a screening instrument used to assess the executive function. Time consumed is recorded as the result, with higher scores indicating greater disease severity.	5 years
Change From Baseline in Geriatric Depression Scale (GDS) at 5 years	GDS is a neuropsychological scale used to assess the level of depression. The total score ranges from 0 to 30, with higher scores indicating greater disease severity.	5 years
Change From multi-modal MRI neuroimaging at 5 years	Evaluation of multimodal MRI, including high-resolution structural T1 imaging, functional MRI, diffusion tensor imaging and quantitative susceptibility mapping.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Blood concentration of Phosphorylated Tau (p-tau) at 5 years	Blood p-tau 181 and p-tau 217 at baseline will be tested. The higher blood p-tau is a strong predictor for AD.	5 years
Change From Baseline in Blood Concentration of Amyloid β (Aβ) at 5 years	Blood Aβ40 and Aβ42 at baseline will be tested. The decreased blood Aβ42/40 ratio is a strong predictor for AD.	5 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Study Chair: Gang Wang, MD, PhD, Ruijin Hospital

Publications and helpful links

General Publications

• Cannon-Albright LA, Foster NL, Schliep K, Farnham JM, Teerlink CC, Kaddas H, Tschanz J, Corcoran C, Kauwe JSK. Relative risk for Alzheimer disease based on complete family history. Neurology. 2019 Apr 9;92(15):e1745-e1753. doi: 10.1212/WNL.0000000000007231. Epub 2019 Mar 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): March 1, 2029
• Study Completion (Anticipated): March 1, 2030

Study Registration Dates

• First Submitted: October 12, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Tauopathies; Alzheimer Disease; Neurodegenerative Diseases; Neurocognitive Disorders
• Other Study ID Numbers: SHARAD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No