Biomarkers of neurodegeneration in schizophrenia: Systematic Review and Meta-Analysis

Abstract

AbstractQuestionDoes neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared to the general population. This may reflect higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer’s disease (AD). Alternatively, this may reflect nonpathological, age-related cognitive decline in a population with low cognitive reserve. We reviewed the literature on neurodegeneration markers in older people with schizophrenia and dementia or cognitive impairment to establish whether neurodegenerative disease underlies the increased rate of dementia observed.Study Selection and AnalysisWe reviewed papers that compared post-mortem findings, hippocampal volume, or CSF markers of AD, in schizophrenia patients with evidence of cognitive impairment (age ≥45 years) with controls. Most studies investigated AD neuropathology. We subsequently performed a meta-analysis of post-mortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired schizophrenia patients to either controls or an AD group.FindingsNo studies found significant increase of amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired schizophrenia patients compared to controls. All postmortem studies that compared APs or NFTs in schizophrenia patients to an AD group found significantly more APs or NFTs in AD. No studies found significant differences in CSF total tau or phosphorylated tau between schizophrenia patients and controls. Two studies found significantly decreased CSF Aβ42 in schizophrenia compared to patients. Findings for hippocampal volume were mixed.ConclusionsStudies have not found higher rates of AD-related pathology in cognitively impaired schizophrenia individuals compared to controls. Higher rates of dementia identified in population studies may reflect lack of specificity in clinical diagnostic tools used to diagnose dementia.