Chronic schizophrenia versus Alzheimer's disease: neuroimaging perspectives on the late-life course of schizophrenia.

Schizophrenia (SCZ) is a chronic mental disorder that typically starts in early adulthood. It is characterised by structural brain abnormalities that occur early in the course of the disease, such as changes in the synapses and alterations in the brain white matter, which consequently progress to brain atrophy in several regions of the brain, as well as white matter lesions. On the other hand, epidemiological evidence indicates improved survival and increased life expectancy among patients with SCZ, largely due to advances in diagnosis and medication management, resulting in a growing number of individuals reaching older age. In addition, several studies have shown accelerated aging and an increased risk of cognitive decline in these patients. Consequently, the healthcare system faces a growing challenge: older adults with chronic SCZ who are at increased risk of dementia (particularly Alzheimer-type dementia). Notably, many individuals with chronic SCZ have several modifiable risk factors for dementia, including obesity, diabetes, elevated low-density lipoprotein cholesterol (LDL), metabolic syndrome, physical inactivity, smoking, and social isolation which may result from a combination of long-term antipsychotic medication, lifestyle factors, and medical comorbidities. These factors overlap substantially with established risk factors for Alzheimer's disease (AD) and may contribute to increased vulnerability to cognitive decline and dementia in later life. The clinical presentation of older adults with chronic SCZ who develop progressive cognitive and functional decline may closely resemble AD, owing to overlapping features such as memory impairment, social withdrawal, psychomotor slowing, and gait disturbances associated with vascular and metabolic comorbidities. Distinguishing these conditions represents a major diagnostic challenge for cognitive neurologists and psychogeriatricians. Therefore, this narrative review critically examines the differential and overlapping neuroimaging features of chronic SCZ and AD to facilitate more accurate clinical assessment and diagnosis in late life.