Transcranial Magnetic Stimulation for Apathy in Mild Cognitive Impairment

NCT03590327 | Completed DMC FDA Device

• 2 other identifiers: D2638-R1115904
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Apathy, a profound loss of initiative and motivation, is often seen in older Veterans with memory problems. Apathy leads to serious health problems, increases dependency, and caregiver burden. If untreated, apathy hastens the progression to frank dementia. In a pilot study, the investigators found that apathy, working memory, and function can be restored using magnetic stimulation in some but not all older Veterans. The reason for this variation is unknown. The investigators propose a three-phase study in 125 older Veterans with mild memory problems. Their motivation, memory, and function will be measured periodically. Veterans with apathy that are eligible for treatment will receive either real or sham magnetic stimulation to the front part of their brain over 20 sessions. Genetic testing and biomarkers will be used to differentiate those who respond to magnetic stimulation from those who do not. Impact on function, quality of life, and rates of progression to dementia will also be studied. A project modification was obtained to conduct a cross-sectional study, the COVID Dementia study. The cross-sectional study will examine the effect of the pandemic on MCI and AD patients and their caregivers ("individual COVID-related factors" such as, personally infected, death of a friend/family member, economic hardship, disruption in care, isolation), barriers to telehealth, caregiver distress, NPS, cognition (including onset of delirium), and function. Our goal is to develop a multi-pronged, remotely deliverable intervention to address consequences of healthcare disruptions in older Veterans with cognitive impairment. Aim 1. To explore the association between COVID-related factors and neuropsychiatric symptoms in individuals with MCI and AD. Hypothesis: The number of COVID-related factors endorsed by caregivers will be positively correlated with the severity of NPI-Q in individuals with MCI and AD. Aim 2. To assess cognition (telephonic version of the Montreal Cognitive Assessment; tMoCA12, and daily function (Functional Activities Questionnaire; FAQ13). Hypothesis: The number of COVID-related factors will be positively correlated with the severity of cognitive and functional deficits in individuals with MCI and AD. Aim 3. To explore the associations among COVID-related factors and caregiver distress. Hypothesis: Caregiver resilience and perceived social support will modify the association between COVID-related factors and severity of distress in caregivers.

Conditions

Apathy; Mild Cognitive Impairment; Transcranial Magnetic Stimulation; Loneliness; COVID; Neuropsychiatric Symptoms

Outcome Measures

Primary Outcomes (1)

• Change in Apathy Evaluation Scale Score

  Range 18-72 Lower score is improvement

  2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months

Secondary Outcomes (2)

• Change in Modified Mini Mental State Examination Score

  2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months

• Change in Conner's Continuous Performance Test Commission Error percentage

  2 weeks, 6 weeks, 6 months, 12 months, 24 months, 36 months, and 48 months

Other Outcomes (4)

• Neuropsychiatric Inventory - Questionnaire

  Through study completion, an average of 1 year

• Functional Activities Questionnaire

  Through study completion, an average of 1 year

• UCLA Loneliness scale

  Through study completion, an average of 1 year

Study Arms (3)

Apathy +, rTMS -

NO INTERVENTION

This arm will be followed without intervention

rTMS

ACTIVE COMPARATOR

This group will be randomized to receive rTMS treatment

Device: Transcranial Magnetic Stimulation

Sham

SHAM COMPARATOR

This group will be randomized to receive sham treatment

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

rTMS

Sham; rTMS

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• meeting the modified Mayo Clinic criteria for MCI
• Having caregivers
• apathy threshold (NPI)
• MMSE 23
• On stable dose of antidepressants for at least a month (if applicable)

You may not qualify if:

• PHASE I
• Uncontrolled diabetes mellitus (Fasting BS\>200mg/dl, HbA1c\>10)
• Renal disease requiring dialysis
• Uncontrolled blood pressure (\>160/100, \<100 systolic)
• Metastatic cancer or undergoing chemotherapy
• Deep venous thrombosis or myocardial infarction in past 3 months
• Uncontrolled malignant cardiac arrhythmia
• Cerebral aneurysm or intracranial bleed in past year
• Unstable angina in past month
• Unstable abdominal or thoracic aortic aneurysm (\>4cm)
• End-stage congestive heart failure
• Taking medications known to increase risk of seizures from 2012 Beers criteria such as bupropion, chlorpromazine, clozapine.
• Taking other medications known to increase risk of seizures such as tricyclic antidepressants.
• Taking ototoxic medications: Aminoglycosides, Cisplatin
• History of seizures/ seizures in first degree relatives

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Central Arkansas Veterans Healthcare System: collaborator
• University of Arkansas: collaborator

Study Sites (1)

Central Arkansas Veterans Healthcare System , Little Rock, AR

Little Rock, Arkansas, 72205, United States

Location

Related Publications (9)

• Sharma T, Padala PR, Mehta JL. Loneliness and Social Isolation: Determinants of Cardiovascular Outcomes. Curr Cardiol Rev. 2021;17(6):e051121190873. doi: 10.2174/1573403X17666210129101845.

  PMID: 33511946 BACKGROUND

• Padala KP, Jendro AM, Wilson KB, Padala PR. Technology Use to Bridge the Gap of Social Distancing during COVID-19. J Geriatr Med Gerontol. 2020 Jun 29;6(2):10.23937/2469-5858/1510092. doi: 10.23937/2469-5858/1510092. No abstract available.

  PMID: 33511321 BACKGROUND

• Padala KP, Parkes CM, Padala PR. Neuropsychological and Functional Impact of COVID-19 on Mild Cognitive Impairment. Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317520960875. doi: 10.1177/1533317520960875.

  PMID: 32969235 BACKGROUND

• Padala PR, Boozer EM, Lensing SY, Parkes CM, Hunter CR, Dennis RA, Caceda R, Padala KP. Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study. J Alzheimers Dis. 2020;77(4):1483-1493. doi: 10.3233/JAD-200640.

  PMID: 32925060 BACKGROUND

• Preston AM, Padala PR. Virtual reality on the verge of becoming a reality for geriatric research. Int Psychogeriatr. 2022 Feb;34(2):97-99. doi: 10.1017/S1041610221000867. Epub 2021 Jun 8. No abstract available.

  PMID: 34099086 BACKGROUND

• Mintzer J, Lanctot KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, Padala PR, Brawman-Mintzer O, Porsteinsson AP, Lerner AJ, Craft S, Levey AI, Burke W, Perin J, Shade D; ADMET 2 Research Group. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA Neurol. 2021 Nov 1;78(11):1324-1332. doi: 10.1001/jamaneurol.2021.3356.

  PMID: 34570180 BACKGROUND

• Mortby ME, Adler L, Aguera-Ortiz L, Bateman DR, Brodaty H, Cantillon M, Geda YE, Ismail Z, Lanctot KL, Marshall GA, Padala PR, Politis A, Rosenberg PB, Siarkos K, Sultzer DL, Theleritis C; ISTAART NPS PIA. Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials. Am J Geriatr Psychiatry. 2022 Feb;30(2):119-147. doi: 10.1016/j.jagp.2021.06.016. Epub 2021 Jul 1.

  PMID: 34315645 BACKGROUND

• Okolichany R, Padala PR, Mooney S. Cognitive and Functional Abilities in an Older Adult Veteran Before and After Contracting COVID-19. J Alzheimers Dis Rep. 2022 Mar 25;6(1):115-120. doi: 10.3233/ADR-210055. eCollection 2022.

  PMID: 35530116 BACKGROUND

• Preston AM, Brown L, Padala KP, Padala PR. Veterans Affairs Health Care Provider Perceptions of Virtual Reality: Brief Exploratory Survey. Interact J Med Res. 2022 Sep 2;11(2):e38490. doi: 10.2196/38490.

  PMID: 36053568 BACKGROUND

MeSH Terms

Conditions

Lethargy; Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Prasad R. Padala, MBBS MBBS

  Central Arkansas Veterans Healthcare System , Little Rock, AR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: July 18, 2018
• Study Start: November 1, 2018
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 25, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)