Genetic and Cognitive Predictors of Aphasia Treatment Response

Laying the Groundwork for Personalized Medicine in Aphasia Therapy: Genetic and Cognitive Predictors of Restorative Treatment Response

Aphasia, or language impairment after a stroke, affects approximately 2 million people in the United States, with an estimated 180,000 new cases each year. The medical community cannot predict how well someone with aphasia will respond to treatment, as some people with aphasia are poor responders to intervention even when participating in empirically supported treatments. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. This study will investigate whether two genes and cognitive abilities, such as memory, predict responsiveness to aphasia therapy for word-retrieval difficulties.

Study Overview

• Status: Active, not recruiting
• Conditions: Aphasia
• Intervention / Treatment: Behavioral: Cued picture-naming therapy

Detailed Description

Incomplete understanding of patient-specific factors that determine whether someone will respond well to language therapy after stroke limits the development of methods to target or account for sources of variability. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. The long-term goal of this line of work is to maximize response to aphasia therapy by incorporating patient-specific factors into decisions related to treatment planning. The overall objective of this application is to identify patterns of patient-specific factors including two candidate genes and cognitive skills that show a relationship with treatment outcomes. The central hypothesis is that there will be a relationship between ApoE and BDNF genotypes, and working memory on stimulus generalization. The rationale for the proposed project is that the identification of factors that impact treatment responsiveness will allow for better estimation of prognosis, improved triage of individuals into appropriate therapy regimens and direct targeting of cognitive factors to maximize behavioral gains. The two specific aims of the project are to determine the degree to which (1) ApoE and BDNF genotypes influence how individuals with aphasia respond to therapy, and (2) working memory abilities are related to stimulus acquisition and stimulus generalization after anomia therapy. Individuals with chronic post-stroke aphasia will undergo cognitive and language assessment, and provide a saliva sample for genetic analysis prior to participating in a cued picture-naming therapy for anomia. The expected outcomes are to integrate cognitive scores and genotypes for BDNF and ApoE into formulating probabilities of individual patient responsiveness to restorative therapy. Improvement in word retrieval abilities will be evaluated using the percentage of pictures named correctly. This contribution is expected to be significant because it will allow for more informed clinical decision making and better allocation of resources to appropriate treatments, thereby making advances in the field toward more personalized medicine, as opposed to a one-size-fits-all clinical approach.

The investigators will determine genotypes for BDNF and ApoE, which will yield four separate groups. At least 20 participants will be enrolled for each genotype group.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least six months post-onset of a single left-hemisphere stroke
• Chronic aphasia
• Anomia (word-retrieval deficits)
• Native English Speaker.

Exclusion Criteria:

• Severe motor speech disorders
• Severe auditory comprehension deficits
• Severe depression.
• Diffuse injury or disease of the brain
• Uncorrected vision or hearing difficulties
• Contraindications for MRI (e.g. cardiac pacemaker, ferrous metal implants, claustrophobia, pregnancy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm Treatment; Cued picture naming therapy will be delivered to all participants. There will be four cohorts of participants based on BDNF and ApoE genotypes.

Behavioral: Cued picture-naming therapy; The proposed study will administer Cued Picture-Naming Treatment (CPNT) four days per week for four weeks (i.e. 16 sessions). During therapy, participants will attempt to name eight consecutive presentations of the same black and white picture, for each of the 20 pictures, with cueing from the administrator. Trials will include (1) independent naming, (2) orthographic cueing (i.e. the written word beneath the picture.), (3) repeating, (4) naming after a short delay (i.e. approximately three seconds), (5)semantic cueing (i.e. three cues providing semantic information about the target will be spoken to the participant by the clinician), (6) phonological cueing (i.e. the first sound and letter will be spoken by the clinician), (7) repeating, and (8) naming after a short delay. The administrator will provide the correct response for each incorrect participant response and will ask the participant to repeat it.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of pictures named correctly	Picture-naming score changes from baseline to post-treatment.	from baseline to 1 month
Percentage of pictures named correctly	Picture-naming score changes from post-treatment to follow up.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of definitions named correctly	Changes in naming pictures trained from definition from baseline to post-treatment	after 1 month
Percentage of untrained pictures named correctly	Changes in naming of untrained items from baseline to post-treatment	after 1 month

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: Nationwide Children's Hospital
• Investigators: Principal Investigator: Stacy M Harnish, PhD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Communication Disorders; Language Disorders; Speech Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Aphasia
• Other Study ID Numbers: 60066189

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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