Brain mechanisms underlying neuropsychiatric symptoms in Alzheimer’s disease: a systematic review of symptom-general and –specific lesion patterns

Neuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.

Neuropsychiatric Features of Neurosyphilis: Frequency, Relationship with the Severity of Cognitive Impairment and Comparison with Alzheimer Disease

Background: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. Objective: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). Methods: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. Results: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). Conclusions: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD.

Mild Cognitive Impairment and predementia syndromes

Mild cognitive impairment is a term used to describe a condition or conditions where subjects have recognisable degrees of objective cognitive impairment which fall short of current standardised definitions for either a dementia syndrome in general, or for particular disorders such as Alzheimer’s disease, dementia with Lewy bodies or frontotemporal dementia. This chapter summarises some of the key issues surrounding the historical development of pre-dementia syndromes, considers the conceptual issues related to the use of the term mild cognitive impairment as a diagnosis, summarises what is known regarding epidemiology, clinical features, pathophysiology, prognosis, therapeutics and outlines current clinical practice in the area. The chapter concludes with a review of recent research developments and looks at the new diagnostic criteria, in particular the potential use of biomarkers to allow diagnosis of Alzheimer’s disease (AD) at an early, or mild cognitive impairment, stage.