Tau Biomarkers in Late-onset Psychosis (LOP)

Hallucinations or delusions that occur for the first time in older people with no acute medical problems or mood symptoms may be related to impending dementia. This study aims to confirm this hypothesis using novel blood biomarkers and Positron Emission Tomography (PET) imaging tracers, as well as non-invasive testing.

Psychotic symptoms that occur in advanced age in the absence of an acute medical condition or prominent mood symptoms can represent the late appearance of primary psychotic disorders such as very late-onset schizophrenia-like psychosis (VLOSP) or delusional disorder, or can presage the appearance of a neurodegenerative condition such as Alzheimer's disease (AD). An episode of non-affective psychosis late in life more than doubles the risk of subsequent neurodegenerative disease, with an average time from psychosis to AD diagnosis of 18 months. The biologic mechanisms responsible for the increased risk of dementia in those who experience psychosis are unclear. One hypothesis is reverse causality, in which inchoate neurodegeneration is responsible for psychotic symptoms that emerge in the absence of traditional cognitive hallmarks of dementia. The psychosis then heralds the inception of illness that will eventuate in cognitive decline. The investigators will utilize neurodegenerative biomarkers in the form of novel PET imaging tracers, plasma immunoassays and non-invasive neurophysiologic measurements to test this hypothesis in a pilot cohort of elderly subjects suffering with psychosis occurring in late-life without dementia for comparison with a cohort of healthy elderly controls (HEC)s who are participating in a study focused on those with dementia.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female, aged 65-85 years.
2. Diagnosis of late-onset non-affective primary psychotic disorder consistent with either very late-onset schizophrenia-like psychosis (VLOSP, International Late-Onset Schizophrenia Group consensus criteria, Howard et al., 2000) or delusional disorder (DSM-5 criteria)
3. Caregiver available to provide collateral history and participation in informant-based ratings (NPI,CDR)
4. Clinical Dementia Rating (CDR) score of 0 or 0.5.
5. Mini-Mental State Examination (MMSE) score ≥ 24 and at the screening visit.
6. Normal memory function (to rule-out mild cognitive impairment, MCI) documented by scoring within 1.5 SD range in education adjusted norms of the Logical Memory II subscale
7. Ability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation (hearing aids permitted).

Exclusion Criteria:

1. Participants with affective and psychotic disorders including bipolar disorder, schizoaffective disorder, active major depression; insulin dependent type 2 diabetes; a history of CVD; a history of epilepsy; a history of TBI with greater than 15 minutes of loss of consciousness; a movement disorder including Parkinson's disease; stroke; autoimmune disease affecting the CNS; substance abuse disorder; or active delirium/encephalopathy.
2. Evidence of a clinically relevant neurological disorder
3. Modified Hachinski ischemia score of more than 4.
4. History of alcoholism or drug dependency/abuse within the last 5 years before screening.
5. Presence of metal implants such as pacemakers, ear implants, internal bullet fragments or shrapnel.
6. Inability to lie flat for 1 hour approximately.
7. Hearing impairment as evidenced by the inability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation. Subjects with hearing aids will be allowed to participate if they meet minimum hearing requirements.