See the full criteria
Inclusion Criteria (all):
* 50-85 years of age, male or female
* Able to give informed consent
* Adequate visual and auditory acuity to complete the neuropsychological testing
* No presence or history of significant neurological or psychiatric disorders
* BDI ≥ 20, moderate depression
* No presence or history of inflammatory or autoimmune disorders
* Negative family history for neurodegenerative diseases
* Cognitively healthy (i.e., education-adjusted MoCA total score ≥ 26 points at screening)
* Female subjects must either be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause) or if they are of childbearing potential, they must commit to use of a highly effective contraceptive measure for the duration of the study and a minimum of six months following the PET scan (including combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence).
* Male subjects and their partners of childbearing potential must commit to the use of a highly effective method of contraception during the study and for a minimum of three months following each PET scan (including, for female partners of childbearing potential, combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, male subjects with vasectomy or sexual abstinence).
* Male subjects must commit to not donate sperm during the study and for a minimum of three months after the last PET scan.
* Individuals must commit to refrain from drinking alcohol for 48 hours before each visit, refrain from drinking any caffeinated substance for 12 hours before the PET-MR visits, and to refrain from smoking or using any nicotine-containing products on the day of the PET-MR scans.
* Individuals must commit to not donating blood up to three months after the last PET scan.
* Individuals must commit to come to the screening and Day 1 visits in a fasting state (i.e., minimum of 8 hours since last meal/food intake).
* Individuals must commit to not to take any over-the-counter non-steroidal anti-inflammatory drugs or drink alcohol for 48h before screening visit.
Inclusion Criteria (Parkinson's disease patients):
* 50-85 years of age, male or female
* Able to give informed consent
* Adequate visual and auditory acuity to complete the neuropsychological testing
* No presence or history of other significant neurological or psychiatric disorders
* Diagnosis of PD according to the Movement Disorder Society Clinical Diagnostic Criteria (Postuma et al., Mov Disord 2015)
* Drug-naïve participants with PD must have a diagnosis of PD but must be therapy-free at the time of enrolment
* For participants with PD-MCI: diagnosis of MCI according the diagnostic criteria for MCI-PD (Level I; Litvan et al., Mov Disord 2012) and/or MoCA \< 23
* For participants with PD taking dopaminergic therapy: must be in stable therapy (i.e. not have changed therapy in the last 60 days)
* Female subjects must either be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause) or if they are of childbearing potential, they must commit to use of a highly effective contraceptive measure for the duration of the study and a minimum of six months following the PET scan (including combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence).
* Male subjects and their partners of childbearing potential must commit to the use of a highly effective method of contraception during the study and for a minimum of three months following each PET scan (including, for female partners of childbearing potential, combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, male subjects with vasectomy or sexual abstinence).
* Male subjects must commit to not donate sperm during the study and for a minimum of three months after the last PET scan.
* Individuals must commit to refrain from drinking alcohol for 48 hours before each visit, refrain from drinking any caffeinated substance for 12 hours before the PET-MR visits, and to refrain from smoking or using any nicotine-containing products on the day of the PET-MR scans.
* Individuals must commit to not donating blood up to three months after the last PET scan.
* Individuals must commit to come to the screening and Day 1 visits in a fasting state (i.e., minimum of 8 hours since last meal/food intake).
* Individuals must commit to not to take any over-the-counter non-steroidal anti-inflammatory drugs or drink alcohol for 48h before screening visit.
For participants with iRBD:
Inclusion criteria:
* 40-85 years of age, male or female
* Able to give informed consent
* Adequate visual and auditory acuity to complete the neuropsychological testing
* No presence or history of significant neurological or psychiatric disorders
* BDI-II ≥ 20, moderate depression
* No presence or history of inflammatory or autoimmune disorders
* Negative family history for neurodegenerative diseases
* Cognitively healthy (i.e., education-adjusted MoCA total score ≥ 26 points at screening)
* Female subjects must either be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause) or if they are of childbearing potential, they must commit to use of a highly effective contraceptive measure for the duration of the study and a minimum of six months following the PET scan (including combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence).
* Male subjects and their partners of childbearing potential must commit to the use of a highly effective method of contraception during the study and for a minimum of three months following each PET scan (including, for female partners of childbearing potential, combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, male subjects with vasectomy or sexual abstinence).
* Male subjects must commit to not donate sperm during the study and for a minimum of three months after the last PET scan.
* Individuals must commit to refrain from drinking alcohol for 48 hours before each visit, refrain from drinking any caffeinated substance for 12 hours before the PET-MR visits, and to refrain from smoking or using any nicotine-containing products on the day of the PET-MR scans.
* Individuals must commit to not donating blood up to three months after the last PET scan.
* Individuals must commit to come to the screening and Day 1 visits in a fasting state (i.e., minimum of 8 hours since last meal/food intake).
* Individuals must commit to not to take any over-the-counter non-steroidal anti-inflammatory drugs or drink alcohol for 48h before screening visit.
Exclusion Criteria (all):
* Unwilling and/or unable to cooperate with study procedures
* Current or a recent (\<12 months) history of drug or alcohol abuse/dependence
* BDI ≥ 20, moderate depression
* Presence of clinically significant (as deemed by the study physician) alterations on safety laboratory blood and urine testing
* Presence of comorbidities or concomitant medications incompatible with the assessment or imaging procedures as deemed by the study physician
* Recent (less than 30 days) use of antipsychotics and corticosteroids
* Recent (less than 2 days) use of NSAIDs.
* Use of any long-acting benzodiazepines (e.g., diazepam) or use of slow or medium acting benzodiazepines with doses ≥ 30 mg within 30 days prior to the first imaging scan.
* Presence of rs6971 genotype of low-affinity binders that hinders the measure of microglial activation with \[11C\]PBR28 PET
* Presence of neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions, signs of inflammation of the CNS
* Presence of serology compatible with HIV, syphilis, SARS-CoV2, or viral hepatitis
* History of autonomic dysfunction, previous vasovagal syncope or a positive tilt-test, and with bradycardia or use of medications causing bradycardia (e.g. beta-blockers)
* Pregnancy or breastfeeding
* Contraindication to MRI, such as presence of metal devises or implants, metal deposited in the body, or metal grains in the eyes
* History of cancer within the last 5 years, except for appropriately treated, non-melanoma skin carcinoma, non-metastatic prostate cancer, treated carcinoma in situ of the cervix or Stage I uterine cancer.
* Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
* Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
* Negative Allen's test (i.e. absence of collateral flow on hands on the test)
* Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
* Concurrent participation to any clinical trial testing investigational drugs
Exclusion Criteria (Parkinson's disease patients):
* Unwilling and/or unable to cooperate with study procedures
* Current or recent history of drug or alcohol abuse/dependence
* BDI ≥ 20, moderate depression
* Presence of clinically significant (as deemed by the study physician) alterations on safety laboratory blood or urine testing
* Presence of comorbidities or concomitant medications incompatible with the assessment or imaging procedures as deemed by the study physician
* Recent (less than 30 days) use of antipsychotics and corticosteroids.
* Recent (less than 2 days) use of NSAIDs.
* Use of any long-acting benzodiazepines (e.g., diazepam) or use of slow or medium acting benzodiazepines with doses ≥ 30 mg within 30 days prior to the first imaging scan.
* Presence of rs6971 genotype of low-affinity binders that hinders the measure of microglial activation with \[11C\]PBR28 PET
* Presence of other neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions, signs of inflammation of the CNS
* History of autonomic dysfunction, previous vasovagal syncope or a positive tilt-test, and with bradycardia or use of medications causing bradycardia (e.g. beta-blockers)
* Presence of serology compatible with HIV, syphilis, SARS-CoV2, or viral hepatitis
* Pregnancy or breastfeeding
* Contraindication to MRI, such as presence of metal devises or implants, metal deposited in the body, or metal grains in the eyes
* History of cancer within the last 5 years, except for appropriately treated, non-melanoma skin carcinoma, non-metastatic prostate cancer, treated carcinoma in situ of the cervix or Stage I uterine cancer.
* Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
* Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
* Negative Allen's test (i.e. absence of collateral flow on hands on the test)
* Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
* Concurrent participation to any clinical trial testing investigational drugs
Exclusion criteria (for participants with iRBD):
* Unwilling and/or unable to cooperate with study procedures
* Current or a recent (\<12 months) history of drug or alcohol abuse/dependence
* BDI-II ≥ 20, moderate depression
* Presence of clinically significant (as deemed by the study physician) alterations on safety laboratory blood and urine testing
* Presence of comorbidities or concomitant medications incompatible with the assessment or imaging procedures as deemed by the study physician
* Recent (less than 30 days) use of antipsychotics and corticosteroids
* Recent (less than 2 days) use of NSAIDs.
* Use of any long-acting benzodiazepines (e.g., diazepam) or use of slow or medium acting benzodiazepines with doses ≥ 30 mg within 30 days prior to the first imaging scan.
* Use of any of the following drugs that might interfere with dopamine transporter SPECT imaging: Ephedrine, ketamine, isoflurane, cocaine, methylphenidate, amphetamine of any amphetamine derivatives, mazindol, modafinil, benztropine, fentanyl, derivatives, buproprion, phentermine neuroleptics, metoclopramide, alpha methyldopa, , reserpine, .
* Presence of rs6971 genotype of low-affinity binders that hinders the measure of microglial activation with \[11C\]PBR28 PET
* Presence of neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions, signs of inflammation of the CNS
* Presence of serology compatible with HIV, syphilis, or viral hepatitis
* History of autonomic dysfunction, previous vasovagal syncope or a positive tilt-test, and with bradycardia or use of medications causing bradycardia (e.g. beta-blockers)
* Pregnancy or breastfeeding
* Contraindication to MRI, such as presence of metal devises or implants, metal deposited in the body, or metal grains in the eyes
* History of cancer within the last 5 years, except for appropriately treated, non-melanoma skin carcinoma, non-metastatic prostate cancer, treated carcinoma in situ of the cervix or Stage I uterine cancer.
* Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
* Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
* Negative Allen's test (i.e. absence of collateral flow on hands on the test)
* Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
* Evidence of presynaptic dopaminergic denervation on \[123I\]FP-CIT SPECT
* Concurrent participation to any clinical trial testing investigational drugs
