Neuropsychological and Neurophysiological Effects of Cognitive Stimulation in Patients With Alzheimer's Disease and Mild Cognitive Impairment

A Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy of a Non-Pharmacological Intervention of Cognitive Stimulation in Subjects With Alzheimer's Disease and Mild Cognitive Impairment: The Brain Stimulation Project.

The present study aims to evaluate the effect of cognitive stimulation (CS) in participants with a diagnosis of moderate and mild Alzheimer's disease (AD) and mild cognitive impairment (MCI) compared to control subjects not receiving any non-pharmacological interventions. Treated participants will receive a structured CS consisting of a wide range of activities aimed at the general improvement of social functioning and the maintenance of cognitive functions. The study consists of a 24-week treatment phase and a follow-up period of 24 weeks. During the treatment period, patients will receive two CS sessions a week. At baseline, all the participants undergo an extensive neuropsychological evaluation and a neurophysiological assessment aimed at studying the frequency of spontaneous blinking (blink rate) and cortical excitability and synaptic plasticity by means of the transcranial magnetic stimulation (TMS). Neuropsychological and neurophysiological evaluations will be repeated at the end of the treatment (week 24) and at the end of the follow-up period (week 48) in order to evaluate short- and long-term effects of CS. The hypothesis of this research is that CS may improve cognition and the neurophysiological parameters studied in treated participants compared to those untreated.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Other: Cognitive Stimulation (CS)

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00185
    • Recruiting
    • Department of Human Neuroscience, Sapienza University of Rome
    • Contact: Carlo de Lena, MD; Phone Number: 0039 0649914028; Email: carlo.delena@uniroma1.it
    • Contact: Alessandro Trebbastoni, MD, PhD; Phone Number: 0039 3491496146; Email: alessandro.trebbastoni@uniroma1.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. moderate AD participants

   • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
   • 1 < Clinical Dementia Rating Scale < 3
   • 13 ≤ Mini-Mental State Examination < 20/30
   • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
   • Geriatric Depression Scale (GDS) ≤ 6

2. mild AD participants

   • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
   • Clinical Dementia Rating Scale = 1 (memory box score ≥ 0.5)
   • 20 > Mini-Mental State Examination < 27/30
   • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
   • Geriatric Depression Scale (GDS) ≤ 6

3. MCI participants

   • Clinical diagnosis of probable AD (National Institute on Aging and Alzheimer's Association criteria)
   • Clinical Dementia Rating Scale < 1 (memory box score ≥ 0.5)
   • Mini-Mental State Examination ≥ 24/30
   • Modified Hachinski Ischaemic Scale (MHIS) ≤ 4
   • Geriatric Depression Scale (GDS) ≤ 6

Exclusion Criteria for all the participants (moderate AD, mild AD and MCI):

• Any medical or neurological condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the subject's cognitive impairment.
• Clinically significant psychiatric illness (e.g., uncontrolled major depression, bipolar affective disorder) within 6 months prior to the enrolment.
• Any medications that, in the opinion of the Investigator, may contribute to cognitive impairment or impair the subject's ability to perform cognitive testing or complete study procedures.
• Contraindications to Transcranial Magnetic Stimulation (history of epilepsy or seizures/presence of pacemaker).
• Subject currently living in an organized care facility with extensive intervention and/or support of daily living activities.
• Inability to comply with study requirements and commitments
• Has not one informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the subject as to be able to provide accurate information about the subject's cognitive and functional abilities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: moderate AD-experimental; Experimental Intervention: The CS shall be carried out in groups (5-7 participants), twice a week. Each session lasts 90 minutes. CS sessions begin with a training for temporal and spatial orientation in which participants are asked to recognize and recall the date and the place with the help of some environmental aids (calendars, clocks, pictures and maps). Then the participants complete an array of cognitive tasks for memory, attention, language, visuo-spatial functions and executive functions. These tasks range from individual paper-and-pencil exercises to verbal-learning exercises that have to be solved by the group.	Other: Cognitive Stimulation (CS); CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
Experimental: mild AD-experimental; Experimental Intervention: the same of the "moderate AD-experimental" arm	Other: Cognitive Stimulation (CS); CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
Experimental: MCI-experimental; Experimental Intervention: the same of the "moderate AD-experimental" arm	Other: Cognitive Stimulation (CS); CS consists of a wide range of structured activities aimed at the general improvement of social functioning and the maintenance of different cognitive functions. It is a non-specific in-group approach that places particular emphasis on social interactions.
No Intervention: moderate AD-placebo
No Intervention: mild AD-placebo
No Intervention: MCI-placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in global cognition as assessed by Mini Mental State Examination	Change from baseline in Mini Mental State Examination score at Week 24 and 48. This scale investigates global cognition. Scale range: 0-30. Normal values >24. Higher values represent a better outcome.	24 and 48 weeks
Change in dementia severity as assessed by Clinical Dementia Rating Scale	Change from baseline in Clinical Dementia Rating Scale score at Week 24 and 48. This scale investigates global cognition and dementia severity. Scale range: 0-5. Normal values = 0. Higher values represent a worse outcome.	24 and 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in frontal functions as assessed by Frontal Assessment Battery	Change from baseline in Frontal Assessment Battery scores at Week 24 and 48. This scale investigates the executive functions. Scale range: 0-30. Normal values ≥ 13.5. Higher values represent a better outcome.	24 and 48 weeks
Change in verbal memory as assessed by Rey Auditory Verbal Learning Test	Change from baseline in Rey Auditory Verbal Learning Test scores at Week 24 and 48. This test investigates verbal learning and memory. Immediate recall scale range: 0-75. Normal values >28.52. Delayed recall scale range: 0-15. Normal values >4.68. Higher values represent a better outcome.	24 and 48 weeks
Change in attention as assessed by Visual Search Test	Change from baseline in Visual Search test score at Week 24 and 48. This test investigates selective attention. Scale range: 0-60. Normal values >30. Higher values represent a better outcome.	24 and 48 weeks
Change in visuospatial functions as assessed by Clock Drawing Test	Change from baseline in Clock Drawing Test score at Week 24 and 48. This test investigates visuospatial abilities and executive functioning. Scale range: 0-61. Normal values >42.17. Higher values represent a better outcome.	24 and 48 weeks
Change in naming as assessed by Boston Naming Test	Change from baseline in Boston Naming test score at Week 24 and 48. This test measure object naming from line drawings. Scale range: 0-60. Normal values >24. Higher values represent a better outcome.	24 and 48 weeks
Change in synaptic plasticity as assessed by Paired Associative Stimulation	Change from baseline in Paired Associative Stimulation at Week 24 and 48. Paired associative stimulation is a paradigm combining peripheral nerve stimulation and transcranial magnetic stimulation over the contralateral primary motor cortex. In healthy humans, Paired Associative Stimulation after-effects last about 30-60 minutes. The extent of facilitatory-Paired Associative Stimulation-induced effects on MEP amplitude ranges from 120% to 160%, while inhibitory-Paired Associative Stimulation may induce a reduction of muscle-evoked potential amplitude that ranges from 60% to 90%.	24 and 48 weeks
Change in blinking as assessed by Blink Rate Evaluation	Change from baseline in the blink rate at Week 24 and 48. Spontaneous blinking was measured by the Blink Rate and was expressed as number of blinks per minute. Normal values: mean Blink Reflex value at rest is 17 blinks/minute; during conversation is 26 blinks/minute; during reading is 4.5 blinks/minute. Cut offs: not applicable.	24 and 48 weeks

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): December 21, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Randomized Controlled Trial; Transcranial Magnetic Stimulation; Cognitive Stimulation; Blink Reflex; Mild Cognitive Stimulation; Non Pharmacological Intervention; Neuropsychological Evaluation
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: BSP-2018

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