Alzheimer's disease and Major Depressive Disorder
Conditions
Interventions
None listed
Sponsors
Gregorio Marañón Hospital
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria (MDD, SZ and AD populations) - Provision of signed and dated informed consent form (ICF) from patient prior to any study-specific procedures being performed. - The patient should have a reliable study partner with whom he/she cohabits or has regular contact with, who gives consent to participate in the study and provide study data (limited to the Neuropsychiatric Inventory for AD patients and the WHO Disability Asessment Schedule (WHODAS) for AD, SZ and MDD patients). - Not socially withdrawn due to external circumstances (e.g. lack of access to transport, rural location) or comorbid medical disorder or disability (e.g., hearing loss, lack of mobility, facial disfigurement). - Patient and study partner must be able to read, write, and speak the language in which assessments are provided. - Unless otherwise stated central nervous system (CNS) medications to treat cognitive impairment due to AD, symptoms of SZ or MDD, and other stable CNS conditions requiring such medication, are permitted provided the patient has been maintained on a stable dose regimen for at least 8 weeks before start of the study, and they are expected to continue this treatment in a stable manner during the current study. Similarly, psychological treatments (e.g., Cognitive Behaviour Therapy, Interpersonal Psychotherapy, Psychodynamic Psychotherapy etc.) are all permitted in this study regardless of frequency and duration, so long as this treatment is expected to remain stable during the duration of the study. - Patient is right-handed or ambidextrous. In the case of ambiguity the Edinburgh Handedness Inventory will be used to determine handedness. Additional inclusion Criteria - AD participants - Men and women aged 50 to 80 years (inclusive). - Probable AD, meeting the National Institute on Aging (NIA) and the Alzheimer*s Association (AA) (NIA-AA) criteria for probable AD - Mini-Mental State Examination (MMSE) score of 20 to 26, inclusive. Additional inclusion Criteria - SZ participants - Patients are male or female, 18-45 years of age (inclusive) with an established diagnosis of schizophrenia according to medical history. - If the patient uses any antipsychotic, anticholinergic or antidepressant medication, dosage needs to be stable for at least 8 weeks prior to the study start. - A DSM-IV diagnosis of SZ with at least one confirmed psychotic episode but not longer than 15 years of disease duration (since first date of established SZ clinical diagnosis). It is, however, preferred and actively encouraged to include patients with a maximum disease duration of 10 years. Additional inclusion Criteria - MDD participants - Male or female, aged 18-55 years of age, inclusive. It is, however, preferred and actively encouraged to include patients aged 45 years and under. - Have a primary Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) diagnosis of MDD without psychotic features, as confirmed by medical history. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder, insomnia or specific phobia may be included. - Meet the DSM-IV criteria for a current Major Depressive Episode. Additional inclusion Criteria - HC participants - Men and women, aged 18-80, inclusive (of s
Exclusion criteria
Exclusion criteria: Exclusion criteria (MDD, SZ and AD populations) Patients cannot enter the study if any of the following exclusion criteria are fulfilled: - Significant neurological disease affecting the CNS, other than AD, SZ, or MDD (e.g. other dementias, serious infection of the brain, Parkinson*s disease, epilepsy) as documented in the patient*s medical file which in the judgement of the investigator may affect the patient's ability to complete the study assessments. - Any other current psychiatric diagnosis, including personality disorders, requiring intervention other than AD, SZ, and MDD according to medical history that in the judgement of the investigator may affect the patient's ability to complete the study assessments. - Current serious or unstable clinically important systemic illness (e.g. hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic, or ocular disorders) that in the judgement of the investigator may affect the patient's ability to complete the study assessments. - History of chronic alcohol or drug abuse or dependence within the previous 3 years. - Participated in any investigational study to treat either AD, SZ, or MDD symptoms or has taken an investigational drug within 90 days (or 5 times the half-life of the investigational drug, whichever is longer). In addition, if they have participated in two or more studies with an experimental drug within 5 months prior to screening. - In the investigator*s judgement is medically non-compliant in the management of their disease. - Has within 6 weeks prior to the first assessment visit been prescribed a medication that may affect the CNS that in the judgment of the investigator may interfere with the patient's ability to complete the study assessments. - Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, pregnancy, or cardiac pacemaker that is not compatible with MRI scanning. - Are, in the opinion of the investigator, likely to present a danger to themselves or others or where the severity of the illness precludes them from completing the study procedures. In the case of high suicidality scores on the QIDS, the study researcher will contact the person who referred the participant to the study. Additional exclusion Criteria - AD participants - Multiple strokes based on history and/or imaging results - A score of 4 or greater on the global Parkinsonism item of the Extrapyramidal Symptom Rating Scale (ESRS) (only relevant to those patients currently taking an antipsychotic medication). - QIDS-SR16 score of >= 16 Additional exclusion Criteria - SZ participants Patients will be excluded from the study if they meet any of the following criteria: - A score of 22 or more on the sum of the 7 PANSS (The Positive and Negative Syndrome Scale) positive symptom factor items. The score of the items of P1 (delusions), P3 (hallucinatory behaviour), P6 (suspiciousness) and G9 (unusual thought content) meet the following requirements: - No more than 2 of the above items have a score of 4. - All of the above items score less than 5. - In the clinician*s judgment, patients who, for any reason, are considered to be a danger to themselves. - QIDS-SR16 score of >= 16 - A score of 4 or greater
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Each objective for this clinical study is associated with specific endpoints. This will enable us to achieve the study objectives and overall goal, to show the reproducibility and generalizability of the quantitative biological parameters which were identified in the original PRISM clinical study (Protocol number ABR59359) as having significant relationships with social dysfunction, in a transdiagnostic manner. Replication Endpoints: 1. To replicate, in a separate cohort, the finding that DMN functional connectivity in the rostromedial prefrontal cortex (rmPFC) on rsfMRI is negatively associated with social functioning in patients with schizophrenia (SZ), Alzheimer*s Disease (AD) and in Healthy Control (HC) participants. Associated endpoints: I. Lower rsfMRI DMN functional connectivity in the rmPFC predicts lower social functioning score (SFS) total scores measured on the same day in patients with AD, SCZ, and in HC, independent of their diagnostic labels. II. Lower rsfMRI DMN functional connectivity in the rmPFC predicts lower De Jong-Gierveld Loneliness Scale (LON) scores measured on the same day in patients with AD, SCZ, and in HC, independent of their diagnostic labels. III. Lower rsfMRI DMN functional connectivity in the rmPFC predicts lower mean cumulative total SFS and LON scores measured on the same day in patients with AD, SCZ, and in HC, independent of their diagnostic labels. 2. To replicate, in a separate cohort, the correlation of SFS self-report social functioning scales with the objective BeHapp measurement of social functioning. Associated endpoints: I. Composite BeHapp scores correlate with SFS total scores across the full range of the scale, independent of study participants* diagnostic labels. The composite BeHapp scores will also be correlated to the total scores from the De Jong-Gierveld Loneliness Scale (LON) for discriminant validity purposes. 3. To replicate, in a separate cohort, the finding that high Behapp socia | — |
Countries
Netherlands
Outcome results
None listed