4 days ago
Systemic Psoriasis Therapy Linked to Less Dementia
SAN DIEGO — While psoriasis is linked to higher rates of dementia, a new study suggested that older patients with psoriasis on systemic treatments may have a much lower risk than those not treated systemically.
In fact, the research hints — but doesn't prove — that the medications could lower the dementia risk even below that of the general population.
The study, which retrospectively evaluated US medical records of people aged 65-95 years from 2004 to 2024, found that patients with psoriasis on systemic therapies (n = 14,679) had a lower risk of developing dementia than those not on systemic treatment (n = 39,601) and lower than a matched general population group (5.77 million).
The adjusted odds ratios (aORs) for the treated psoriasis group vs the untreated group were 0.49 (0.39-0.61) for Alzheimer's disease, 0.65 (0.51-0.83) for vascular dementia, and 0.60 (0.53-0.68) for nonvascular dementia. For the treated group vs the matched general population, the aORs were 0.69 (0.54-0.86), 0.85 (0.65-1.10), and 0.85 (0.75-0.97), respectively.
The findings, presented at the Society for Investigative Dermatology (SID) 2025 Annual Meeting, are too preliminary to affect clinical practice. But the study does add to 'a growing body of evidence linking chronic inflammation to neurodegeneration,' study lead author Madison Olexson, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, Virginia, told Medscape Medical News .
'It reinforces [how] treating systemic diseases like psoriasis may not only improve cutaneous symptoms but may have extra-cutaneous benefits as well,' she said.
Sparse Data on Systemic Treatments and Psoriasis
Several international reports have linked psoriasis with dementia, including a 2019 study that found an elevated risk associated with the skin disease and vascular dementia (hazard ratio [HR], 1.73; 95% CI, 1.21-2.47) and a 2023 study that identified an increased risk for dementia (HR, 1.24; 95% CI, 1.14-1.35). Also, a 2019 study linked dementia to a higher risk for psoriasis (OR, 1.46).
Other autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease have also been linked to higher incidence and risk for cognitive impairment and dementia, Olexson said. 'This is believed to be linked to systemic inflammation and the sustained activity of proinflammatory cytokines such as [tumor necrosis factor] TNF alpha and [interleukin 17] IL-17, which can affect the brain and potentially lead to neurodegeneration. However, the exact mechanisms remain unclear.'
She added that 'it's still a mystery whether psoriasis alone drives the development of dementia or if the increased likelihood is due to shared comorbidities or overlapping inflammatory pathways. Furthermore, we don't yet fully understand whether treatments provide direct cognitive protection or how long treatment needs to continue for maximal benefit.'
Biologics and Non-Biologics Both Linked to Benefit
The researchers launched the new study 'to address the limited and inconsistent data on whether psoriasis associates with dementia outcomes and systemic treatments for psoriasis could influence the likelihood of developing dementia,' Olexson said.
The study retrospectively tracked patients via the TriNetX research network database. Before propensity score matching, the mean age was 66.6 ± 8.9 years for non-treated patients and 67.8 ± 9.0 years for the general population.
Respectively, the groups were 42.8% and 51.7% women and 65.9% and 72.6% White. Data for the treated psoriasis group were not provided, but Olexson said their characteristics were similar.
The study included both biologic medications, which target specific immune pathways, and non-biologic systemic treatments. Patients were treated for a median of 4 years (for both). The biologics were adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, ustekinumab, guselkumab, tildrakizumab, risankizumab, secukinumab, ixekizumab, and brodalumab. The non-biologic treatments were methotrexate, apremilast, acitretin, and ultraviolet phototherapy.
Both drug classes were linked to lower risks for dementia at roughly the same rates, but it was not clear if specific medications may have greater effects.
Less Inflammation May Protect Against Dementia
The adjusted incidence rates of Alzheimer's disease were 1.9% vs 1.2% in the non-psoriasis group vs the treated psoriasis group. For vascular dementia, the rates were 1.2% vs 0.74%, respectively. For nonvascular dementia, they were 5.4% vs 3.7%, respectively.
For untreated patients with psoriasis vs treated patients with psoriasis, the adjusted incident rates were 1.7% and 0.84% for Alzheimer's disease, 1.1% and 0.72% for vascular dementia, and 5.1% and 3.1% for nonvascular dementia, respectively, which Olexson reported were statistically significant differences.
'Systemic therapies likely reduce neuroinflammation by suppressing inflammatory cytokines like TNF alpha and IL-17, both of which have been implicated in neurodegenerative processes,' Olexson said. 'These cytokines can disrupt the blood-brain barrier, promote amyloid beta accumulation, and impair neuronal function. By modulating this inflammatory cascade, systemic treatments may protect against or slow the onset of dementia.'
Findings Are 'Intriguing' but Not Definitive
Asked to comment on the results, Steven R. Feldman, MD, PhD, professor of dermatology, Wake Forest University, Winston-Salem, North Carolina, who was not involved in the study, noted that while the findings are 'intriguing,' they come with caveats because of the observational study design.
'If patients with dementia aren't bothered by their psoriasis or aren't given biologics for that or some other reason, getting a biologic might be associated with less dementia,' he said in an interview. 'It may be that having or not having dementia determines to some degree who gets a biologic, not that taking a biologic determines who gets dementia.'
Olexson agreed that the observational design has limitations. While cohorts were matched by demographics, body mass index, and several comorbidities, she said other factors such as disease severity, socioeconomic status, and access to care could play a role in the findings.
What's next? Moving forward, Olexson said, 'We have plans to conduct prospective studies related to psoriasis and cognitive health at our institution.'
