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.

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.