Β-Amyloid Burden is Not Associated with Cognitive Impairment in Schizophrenia: A Systematic Review

Abstract

Current literature suggests that the pathology of schizophrenia (SCZ) has developmental origins. However, the neurodevelopmental theory of SCZ cannot solely explain several progressive neurodegenerative processes in the illness. There is evidence of accelerated cognitive decline and increased risk of developing dementia in elderly patients with SCZ. Investigating beta-amyloid (Aβ) as a measure of neurodegeneration, we conducted a systematic review focusing on Aβ in patients with SCZ. An OVID literature search using PsychINFO, Medline and Embase database was conducted, looking for studies that compared Aβ levels between patients with SCZ and either elderly controls, patients with AD, or patients with other psychiatric illnesses. Among 14 identified studies, 11 compared Aβ levels between SCZ and elderly controls, seven between SCZ and AD, three between SCZ and other psychiatric illnesses. As a result, no evidence was found suggesting that Aβ levels differ in patients with SCZ from elderly controls or patients with other psychiatric illnesses. All of the seven studies reported lower cortical Aβ levels in patients with SCZ than patients with AD. Furthermore, three out of the four studies, which investigated the relationship between Aβ levels and cognitive impairment in SCZ, observed no association between two factors. The limitations of the included studies are small sample sizes, the inclusion of CSF Aβ or postmortem plaques rather than cortical Aβ assessment in-vivo, and the investigation of different brain regions. In conclusion, Aβ deposition is not associated with cognitive decline in late-life SCZ. Future studies should investigate other neurodegenerative indicators such as oxidative stress and apoptosis dysregulation in SCZ to better understand the pathophysiological mechanisms underlying this illness.

Episodic memory and delayed recall are significantly more impaired in younger patients with deficit schizophrenia than in elderly patients with amnestic mild cognitive impairment

“…Interestingly, a recent review shows that the amyloid cascade is not associated with neurocognitive impairments in schizophrenia [ 41 ]. In MCI, however, low memory and MMSE scores are significantly associated with amyloid positivity [ 42 , 43 ], while increased cerebro-spinal fluid amyloid β42 and t-Tau are the best predictors of conversion from MCI to AD [ 43 ]. Moreover, impairments in episodic memory in schizophrenia may be due to the lack of awareness [ 44 ], while cognitive impairments in MCI may represent deficits that may be associated with incipient dementia [ 45 ].…”

Transgenerational Interaction of Alzheimer’s Disease with Schizophrenia through Amyloid Evolvability

“…2A). Furthermore, it was recently shown that there were no associations between Aβ and cognitive impairment in SCZ [12]. Given that the previous studies were performed using small sample sizes, and Aβ was assessed in cerebrospinal fluid (CSF) rather than cortical region in brain, additional analyses of different brain regions may be required [12].…”

Risk of dementia associated with psychotic disorders in later life: the health in men study (HIMS)

“…Although the cognitive deficits afflicting people with schizophrenia-like psychosis seem to meet criteria for the clinical diagnosis of dementia in later life (de Vries et al 2001), it is not known whether they are caused by pathologies that commonly cause dementia (e.g. Alzheimer's disease, vascular disease) or whether they are caused by the disease underpinning the psychosis or its associated behaviours and treatments (Chung et al 2016).…”