Syphilis reactivity potentially associated with dementia

The rate of syphilis reactivity appears to be higher in individuals with dementia compared with those without the condition, a Singapore study has found.

The population of this retrospective study consisted of 1,271 patients who attended memory clinics at National University Hospital, Singapore between February 2006 and 2016, of whom 745 were diagnosed with dementia (mean age 76 years, 56.9 percent female, median MMSE* score 15). These patients and the 526 patients who attended the memory clinic but did not have dementia (mean age 70 years, 55.7 percent female, median MMSE score 24) were compared with 872 community-dwelling individuals enrolled in the Epidemiology of Dementia in Singapore (EDIS) study (mean age 69 years, 50.7 percent female, median MMSE score 25). Of the memory clinic patients, 4.5 percent (n=57) were syphilis reactive.

Syphilis reactivity was more common in individuals with dementia (5.9 percent, n=44) compared with those without dementia be it among memory clinic patients (2.5 percent, n=13; p=0.004) or those in the community-dwelling EDIS cohort (2.4 percent, n=21; p<0.001). Prevalence of syphilis reactivity was comparable between individuals without dementia in the memory clinic and EDIS study (p>0.05). [Int J STD AIDS 2018;doi:10.1177/0956462418787627]

After adjusting for age, sex, and education, syphilis reactivity was independently associated with dementia among patients in the memory clinic (adjusted odds ratio [OR], 2.06, 95 percent confidence interval, 1.02–4.17; p=0.044).

Conversely, there was no association between syphilis reactivity and any markers of cerebrovascular disease namely cortical stroke (OR, 0.77; p=0.736), lacunae (OR, 1.36; p=0.481), or significant white matter hyperintensities (OR, 0.87; p=0.759), or with markers of neurodegeneration namely significant central atrophy (OR, 1.14; p=0.777), cortical atrophy (OR, 1.65; p=0.364), or medial temporal lobe atrophy (OR, 1.47; p=0.450).

“Syphilis is one of the treatable causes of cognitive impairment and dementia,” said the researchers. “Syphilis can be easily treated with antibiotics but the underdetection and treatment failure of syphilis may lead to multisystem damage and possibly increase the risk of concomitant neurological impairments,” they said. [Arch Dermatol 2001;137:1373-1374]

“Therefore, the presence of syphilis reactivity in patients with dementia may suggest a need for earlier detection and treatment,” they said.

“Neuropathological studies have shown infiltration of spirochetes into brain tissue may cause degeneration, fibrosis, and gradual narrowing of cerebral blood vessels. Such degeneration may increase permeability of the blood-brain barrier leading to vasogenic and cytotoxic oedema, which, if not treated, may at a later stage undergo irreversible atrophy. Similarly, fibrosis and gradual narrowing of blood vessels cause hypoperfusion in brain tissue; such chronic hypoperfusion leads to cerebral atrophy, lacunae, infarcts, and white matter hyperintensities,” added the researchers. [Handb Clin Neurol 2008;89:825-844; Neurocase 2017;23:82-83; BMC Neurol 2012;12:96; Chin Med J 2003;116:1051-1054; AJNR Am J Neuroradiol 1995;16:703-711]

“[As] both cerebrovascular disease and neurodegeneration were not associated with syphilis reactivity … we propose a hypothesis for further study that neuroinflammation may be the cause of cognitive impairment and dementia in syphilis reactive patients,” they said, highlighting the mechanism of the association between syphilis and vascular cognitive impairment, neurodegeneration, and dementia as another potential scope for research.