Alzheimer’s Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers

Abstract

Background: Neurosyphilis-associated cognitive and behavioral impairment— historically coined as “general paralysis of the insane”— share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer’s disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-β deposition. Consequently, accurate classification and timely differential diagnosis may be challenging. Objective: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy. Methods: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases. Results: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD. Conclusion: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.

Neutrophil CD64 index as a potential blood biomarker for the diagnosis of neurosyphilis in secondary and tertiary syphilis: A retrospective study

“…Of symptomatic cases, neurosyphilis could mimic many other neurological diseases, which may lead to significant diagnostic delay in patients without previous known history of syphilis. The most common clinic neurosyphilis manifestations of dementia, psychosis, and cognitive impairment are also observed in primary psychosis [ 20 ] and neurodegenerative diseases such as Alzheimer's disease [ 21 ], Parkinson's Disease and Huntington Disease etc [ 10 , 22 ]. Hence, the laboratory examination is of great importance for the diagnosis and differential diagnosis of neurosyphilis.…”

“…Besides, some patients with no-obvious symptoms usually refuse to take the lumbar puncture considering the invasive operation, which may lead to the missed detection of early and asymptomatic NS [ 8 , 9 ]. What's more, as the great imitator, neurosyphilis can mimic many psychiatric and neurological diseases and leads to the diagnostic delay in patients without previous known history of syphilis [ 10 , 11 ]. Thus, it is in great demand to look for other indicators which are easy to determine and have better performance in NS diagnosis.…”