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The following is a summary of “Association of Neurogranin and BACE1 With Clinical Cognitive Decline in Individuals With Subjective Cognitive Decline,” published in the September 2024 issue of Neurology by Wang et al.

Cerebrospinal fluid (CSF) biomarkers, which have significant diagnostic and prognostic potential for Alzheimer’s disease (AD), are currently used to detect the disease relatively late, prompting the search for additional biomarkers to identify preclinical pathology and predict cognitive decline.

Researchers conducted a retrospective study assessing the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD). 

They enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of the Preclinical Alzheimer’s Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as the conversion of SCD to mild cognitive impairment (MCI) during follow-up. Neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively. 

The results showed 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were, the rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = −0.138, SE = 0.065, P=0.037, and β = −0.293, SE = 0.115, P=0.013). Higher baseline neurogranin and neurogranin/BACE1 ratios were associated with an increased rate of conversion from SCD to MCI (HR 1.35 per SD, 95% CI 1.03–1.77, P=0.028, and HR 1.53 per SD, 95% CI 1.13–2.07, P=0.007). In addition, the impact of higher neurogranin levels on accelerating the rate of cognitive decline was more pronounced in the SCD group than in cognitively unimpaired controls (β = −0.077, SE = 0.033, P=0.020). 

They concluded that CSF neurogranin and BACE1 began to change in the preclinical stage of AD and were associated with clinical progression in individuals with SCD. 

Source: neurology.org/doi/10.1212/WNL.0000000000209806