Cognition in Patients With Hypoglycemia, Without Diabetes

Completed

Conditions: Cognition
Hypoglycemia

Interventions: Other: Cognitive Assessment (not diagnostic)
Diagnostic Test: ECG

Registration Number: NCT04430582

Lead Sponsor: Joslin Diabetes Center

Brief Summary: The purpose of this study is to determine if there are differences in cognitive function (thinking) in individuals who have recurrent hypoglycemia (low blood sugars) following Roux-en-Y gastric bypass, compared with individuals who have also had a Roux-en-Y gastric bypass but do not have hypoglycemia.

Detailed Description: This study will test the hypothesis that a history of recurrent hypoglycemia following gastric bypass is associated with differences in cognition (thinking), by analyzing results of cognitive testing in post-gastric bypass individuals with a history of hypoglycemia as compared to those without known hypoglycemia.

This pilot study will identify cognitive domains of interest, as well as inform the development of a future battery of assessments, which could be replicated in a larger sample. Cognitive domains which will be assessed include: premorbid intelligence, memory, language, executive function, and psychomotor speed.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

Inclusion Criteria

Age 18-70 years of age, inclusive, at screening.
Willingness to provide informed consent and attend one study visit.
For hypoglycemia after upper GI surgery group: Males or females diagnosed with ongoing post upper GI surgery hypoglycemia, with prior episodes of neuroglycopenia, unresponsive to dietary intervention.
For hypoglycemia without a history of upper gastrointestinal surgery group: Males or females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia, and without a history of prediabetes, diabetes, or upper GI surgery.
For post-bariatric without hypoglycemia group: Males or females with history of bariatric surgery, and no history of symptomatic hypoglycemia.
For non-surgical controls only: Males or females with no history of upper GI surgery and no history of hypoglycemia, prediabetes, or diabetes.

Exclusion Criteria

Active treatment with any diabetes medications, except for acarbose.
History of cerebrovascular accident.
History of a traumatic brain injury not related to hypoglycemia.
Active depression.
Active alcohol abuse or substance abuse.
Known insulinoma, gastrinoma or other neuroendocrine tumor.
Having undergone same / similar cognitive assessments within the last calendar year.

There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hypoglycemia after upper gastrointestinal (GI) surgery	ECG	Participants with hypoglycemia after upper GI surgery, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.
Controls, no hypoglycemia or history of upper GI surgery	Cognitive Assessment (not diagnostic)	Participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement. Some participants may be recruited from other hypoglycemia studies at Joslin.
Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM	ECG	Participants with hypoglycemia and no history of upper gastrointestinal surgery, and NO current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, or from other hypoglycemia studies at Joslin.
Hypoglycemia after upper gastrointestinal (GI) surgery	Cognitive Assessment (not diagnostic)	Participants with hypoglycemia after upper GI surgery, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.
Asymptomatic post-bariatric participants	Cognitive Assessment (not diagnostic)	Participants with a history of bariatric surgery, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia. They will be recruited by advertisement flyers at postoperative surgical clinics at local hospitals (e.g. Brigham and Women's and Beth Israel Deaconess Hospitals) and from other hypoglycemia studies at Joslin.
Hypoglycemia no upper GI surgery & no diabetes (DM) or pre-DM	Cognitive Assessment (not diagnostic)	Participants with hypoglycemia and no history of upper gastrointestinal surgery, and NO current diagnosis of diabetes or pre-diabetes, recruited from the Joslin Hypoglycemia Clinic, or from other hypoglycemia studies at Joslin.
Controls, no hypoglycemia or history of upper GI surgery	ECG	Participants without hypoglycemia or upper gastrointestinal surgery (controls), recruited by local advertisement. Some participants may be recruited from other hypoglycemia studies at Joslin.
Asymptomatic post-bariatric participants	ECG	Participants with a history of bariatric surgery, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia. They will be recruited by advertisement flyers at postoperative surgical clinics at local hospitals (e.g. Brigham and Women's and Beth Israel Deaconess Hospitals) and from other hypoglycemia studies at Joslin.

Primary Outcome Measures

Name	Time	Method
Assessment of Immediate Verbal Memory	During the one day of cognitive assessment administration.	Rey Auditory Verbal Learning Test (RAVLT) immediate recall accuracy scores was used to measure immediate verbal memory. Scores for this assessment were compared between groups. Scores for this assessment range 0 to 69, with a higher score indicating a superior immediate verbal memory. Wilcoxon rank-sum tests was used to examine differences between groups.
Assessment of Delayed Verbal Memory	During the one day of cognitive assessment administration.	RAVLT 20 minute recall accuracy scores, was used to measure delayed memory and was compared between groups. Scores for this assessment range 0 to 15, with a higher score indicating less delays in memory. Wilcoxon rank-sum tests was used to examine differences between groups.
Working Memory Assessed by the Letter Number Sequencing Scaled Score	During the one day of cognitive assessment administration.	Letter-Number Sequencing subtest from the Wechsler Memory Scale III scaled scores were used to measure working memory and were compared between groups. Wilcoxon rank-sum test was used to examine differences between groups. Scores for this assessment range 1 to 19, with a higher score indicating a superior working memory.

Secondary Outcome Measures

Name	Time	Method
Assessment of Cognitive Flexibility Using Trails Scaled Score	During the one day of cognitive assessment administration.	Delis-Kaplan Executive Function System (DKEFS),Trail Making Task score was used to assess the cognitive flexibility component of executive function. Scores are derived from time to complete the task plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive flexibility.
Assessment of Cognitive Flexibility Using Color-word Inference Test	During the one day of cognitive assessment administration.	DKEFS Color-Word Interference Test (CWIT) Inhibition Switching scores was used to measure the cognitive flexibility component of executive function. The CWIT is scored by time to complete plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive flexibility.
Assessment of Inhibition Using Color-word Inference Test	During the one day of cognitive assessment administration.	DKEFS CWIT scores was used to measure the inhibition component of executive function. The CWIT is scored by time to complete plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior inhibition.
Verbal Ability Cognitive Control Assessed by Letter Fluency	During the one day of cognitive assessment administration.	DKEFS Letter Fluency Task will be used to assess the verbal functioning cognitive control ability component of executive function. Scores are derived from the number of unique, correct words. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior verbal functioning cognitive control ability.
Assessment of Psychomotor Speed	During the one day of cognitive assessment administration.	The grooved pegboard test is a manipulative dexterity task that assesses psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 25 grooved pegs into holes within the given time limit up to 300 seconds (the score upper limit is thus 300). Time taken to complete the test has been found to be inversely correlated with cognitive ability; therefore, a higher score represents an inferior score. Wilcoxon rank-sum test was used to examine differences between groups.
Verbal Ability Cognitive Control Assessed by Category Fluency	During the one day of cognitive assessment administration.	DKEFS Category Fluency scores were used to measure cognitive control of verbal ability, specifically measuring an individuals ability to access and retrieve semantic information (memory) as a component of executive function. Category fluency is scored by number of correct words plus errors in a 60 second trial in each of 3 categories. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.
Verbal Ability Cognitive Flexibility, Assessed by Category Switching Scaled Score	During the one day of cognitive assessment administration.	DKEFS Category Switching scores will be used to measure cognitive control of verbal ability, specifically measuring an individuals ability to access and retrieve semantic information (memory), switching back and forth between 2 different semantic categories, a component of executive function. Category switching is scored by number of correct words plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.
Verbal Ability Cognitive Control of Inhibition, Assessed by Category Switching Accuracy Scaled Score	During the one day of cognitive assessment administration.	DKEFS Category Switching Accuracy scores will be used to measure cognitive control of verbal ability, specifically measuring an individuals ability to inhibit incorrect or repetitive semantic information (memory), while switching back and forth between 2 different semantic categories, a component of executive function. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.
Lexical Processing Assessed by Letter Fluency, First Interval.	During one day of cognitive assessement administration.	DKEFS Letter Fluency, first interval scores will be used to measure cognitive control of lexical processing, specifically measuring an individuals ability to retrieve phonemic information, a component of executive function. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. There are four intervals of this task the first assessing initiation of retrieval while the following trials measuring the ability to sustain retrieval. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of lexical processing.
Lexical Processing as Assessed by Letter Fluency, Second Interval	During one day of cognitive assessement administration.	DKEFS Letter Fluency, second interval scores will be used to measure cognitive control of lexical processing, specifically measuring an individuals ability to retrieve phonemic information, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to sustain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of lexical processing.
Lexical Processing Assessed by Letter Fluency, Third Interval	During one day of cognitive assessment administration.	DKEFS Letter Fluency, third interval scores will be used to measure sustainment of cognitive control of lexical processing, specifically measuring an individuals ability to continue to retrieve phonemic information after multiple trials, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to maintain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior sustainment of cognitive control of lexical processing.
Lexical Processing Assessed by Letter Fluency, Fourth Interval	During one day of cognitive assessment administration.	DKEFS Letter Fluency, fourth interval scores will be used to measure sustainment of cognitive control of lexical processing, specifically measuring an individuals ability to continue to retrieve phonemic information after multiple trials, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to maintain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior sustainment of cognitive control of lexical processing.