CSF conversion assay identifies cognitive impairment due to probable Lewy body disease

A cerebrospinal fluid alpha-synuclein real-time, quaking-induced conversion assay demonstrated efficacy as a “robust biomarker” for identifying mild cognitive impairment due to probable Lewy body disease, according to researchers.

To date, no study has investigated the diagnostic value of the assay — abbreviated as -syn RT-QuIC — in patients with mild cognitive impairment, “representing a common prodromal clinical manifestation of [dementia with Lewy bodies],” they wrote. “Indeed, following the strategies implemented for [Alzheimer’s disease], the diagnostic research criteria for [dementia with Lewy bodies] have been recently expanded to include patients in the prodromal stage. Despite this, however, current research criteria for [mild cognitive impairment due to probable Lewy body disease], in contrast to those for [mild cognitive impairment-AD], do not consider any biofluid molecular markers.”

Marcello Rossi, MSc, of the IRCCS Institute of Neurological Sciences of Bologna, and colleagues aimed to “fill this gap” in the research by determining whether an -syn RT-QuIC accurately identified patients with mild cognitive impairment due to probable Lewy body disease. The researchers applied this conversion assay to 289 samples of CSF that were obtained from two independent cohorts. The cohorts included 81 patients with mild cognitive impairment due to probable Lewy body disease (70.7±6.6 years; 13.6% women; mini-mental state examination, 26.1±2.4), 120 with probable mild cognitive impairment-AD (68.6±7.4 years; 45.8% women; mini-mental state examination, 25.5±2.8) and 30 with unspecified mild cognitive impairment (65.4±9.3 years; 30% women; mini-mental state examination, 27±3). The study also included 58 individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals without brain alpha-synuclein deposits upon neuropathological examination as controls.

The conversion assay identified patients with mild cognitive impairment due to probable Lewy body disease against cognitively unimpaired controls with 95% sensitivity, 97% specificity and 96% accuracy, according to the study results. The conversion assay also demonstrated 98% specificity in neuropathological controls.

Rossi and colleagues found that the accuracy of the test for mild cognitive impairment due to probable Lewy body disease was consistent between the two cohorts (97.3% vs. 93.7%). They also found that 13% of patients with mild cognitive impairment-AD had a positive test, noting that 44% of these patients developed “one core or supportive clinical feature” of dementia with Lewy bodies at follow-up. The latter results suggested “an underlying Lewy body co-pathology,” according to the study results.

“Taken together, these findings are in line with preliminary results obtained in patients with isolated REM sleep behavior disorder, pure autonomic failure and those with incidental [Lewy body dementia] at post-mortem examination, demonstrating that patients with [Lewy body dementia] harbor significant [alpha-synuclein] seeding activity early in the course of the disease, irrespective of clinical presentation,” the researchers wrote. “Consequently, the detection of abnormal [alpha-synuclein] species by RT-QuIC is not only very accurate but also represents an early biomarker for [Lewy body dementia].”

Rossi and colleagues noted that the current findings should be validated in “an inter-laboratory setting” and confirmed in larger cohorts that include “less stringent” selection criteria as well as long follow-up or postmortem confirmation to determine the clinical predictive value of the -syn RT-QuIC and its value compared with current criteria and biomarkers.

“[This] novel biomarker accurately identified [dementia with Lewy bodies in patients] at the prodromal clinical stage and demonstrated high specificity in a large cohort of individuals examined neuropathologically,” the researchers wrote. “Thus, its implementation after validation may help the clinical management and recruitment for clinical trials in memory clinics.”