| Eligibility |
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.
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
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