Biomarkers of neurodegeneration in schizophrenia: systematic review and meta-analysis

Abstract

Question: Does 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 with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.

Study selection and analysis: We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group.

Findings: No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aβ42 between patients with schizophrenia and controls found significantly decreased CSF Aβ42 in schizophrenia compared with controls. Hippocampal volume findings were mixed.

Conclusions: Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.

Keywords: Schizophrenia & psychotic disorders.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 flow diagram for new systematic reviews which included searches of databases and registers only.

Figure 2

Density of amyloid plaques in schizophrenia versus Alzheimer’s. Forest plot showing the effect size (Hedge’s G) and the pooled effect size for studies comparing amyloid-β plaques in the schizophrenia group (‘experimental’) versus Alzheimer’s disease (‘controls’). ‘Total’ denotes the sample size and SMD denotes standardised mean difference.

Figure 3

Density of neurofibrillary tangles (NFTs) in schizophrenia versus Alzheimer’s. Forest plot showing the effect size (Hedge’s G) and the pooled effect size for studies comparing NFTs in the schizophrenia group (‘experimental’) versus AD (‘control’). ‘Total’ denotes the sample size and SMD denotes standardised mean difference.

Figure 4

Density of amyloid plaques in schizophrenia versus controls. Forest plot showing the effect size (Hedge’s G) and the pooled effect size for studies comparing amyloid-β plaques in the schizophrenia group (‘experimental’) versus normal controls (‘controls’). ‘Total’ denotes the sample size and SMD denotes standardised mean difference.

Figure 5

Density of neurofibrillary tangles (NFTs) in schizophrenia versus controls. Forest plot showing the effect size (Hedge’s G) and the pooled effect size for studies comparing NFTs in the schizophrenia group (‘experimental’) versus normal controls (‘control’). ‘Total’ denotes the sample size and SMD denotes standardised mean difference.