High CSF Neurogranin Associated With Faster Decline in Mild Cognitive Impairment

High levels of postsynaptic protein neurogranin in the cerebrospinal fluid (CSF) are independently associated with poor and declining memory in patients with mild cognitive impairment (MCI), according to study findings published in Neurology.

Investigators obtained data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database on patients with normal cognition (n=111) and MCI (n=193), all of whom had CSF Ng samples at baseline as well as memory and executive function evaluations at follow-up. At baseline, a greater percentage of patients with MCI were carriers of APOE ε4 (53% vs 24%, respectively; P <.001), had lower Mini-Mental State Examination (MMSE) scores (27+/−2 vs 29+/−1, respectively; P <.001), higher CSF Ng (494±353 pg/mL vs 352±294 pg/mL, respectively; P <.001), lower Aβ₄₂ (166±54 pg/mL vs 206±55 pg/mL, respectively; P <.001), and greater t-tau (102±60 pg/mL vs 69±30 pg/mL, respectively; P <.001).

Participants with higher CSF Ng levels scored significantly worse on baseline memory compared with participants with lower CSF Ng (β = −0.21; P <.0001). In addition, CSF Ng levels were also significantly associated with long-term declines in memory and executive function (β = −0.0313; P =.0068 and β = −0.0346; P =.0169, respectively), associations that were independent of age, education, sex, and APOE ε4 status.

Also, patients presenting with intermediate or high CSF Ng levels demonstrated faster declines in memory compared with participants in the lowest CSF Ng tertile. When investigators controlled for tau and amyloid β₄₂, there was no apparent association between CSF Ng and baseline memory scores 4 (β = 0.01; P =.786).

Selection bias was possible for this sample population due to the convenience sampling of volunteers in this cohort. In addition, the findings of this analysis are limited to associations between Ng and Alzheimer’s Disease Assessment Schedule Cognition 11 and 13, MMSE, and Clinical Dementia Rating (CDR) Sum of Boxes scores and may not be applicable to other measures of cognitive function.

Based on the findings, the investigators suggest “that elevated CSF Ng levels are especially related to the pathologic process of cognitive impairment in the early stage of the disease.”

Reference

Headley A, De Leon-Benedetti A, Dong C, et al. Neurogranin as a predictor of memory and executive function decline in MCI patients. Neurology. 2018;90(10):e887-e895.