Homocysteine - A predictor for five year-mortality in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia.

Background: Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI) are preclinical stages of Alzheimer's Disease (AD), which is the most common entity of dementia. Homocysteine is an amino acid in the methionine cycle, and many studies revealed a significant association between elevated homocysteine serum levels and the progression of dementia. The primary objective of this retrospective study was to investigate whether elevated homocysteine serum levels could be associated with mortality and neuropsychological test results in individuals suffering from SCD, MCI or AD.

Methods: This study is a single-center explorative retrospective data analysis with 976 data protocols from the Memory Outpatient's Clinic of the Medical University of Vienna included. All patients underwent a neurological examination, a laboratory blood test, and neuropsychological testing to establish a diagnosis of either SCD, MCI, or AD. Data was evaluated by Kaplan-Meier functions, factor analysis, and binary logistic regression models.

Results: Patients with AD showed significantly higher mean homocysteine levels (SCD 12.15 ± 4.71, MCI 12.80 ± 4.81, AD 15.0 ± 6.44 μmol/L) compared to those with SCD and MCI (p ≤ .001). The mean age of patients with AD (75.2 ± 7.8) was significantly older at the time of testing than of patients with MCI (69.1 ± 9.6) or SCD (66.8 ± 9.3). Since homocysteine levels increase with age, this could be a possible explanation for the higher levels of AD patients. The age at death did not differ significantly between all diagnostic subgroups, resulting in the shortest survival times for AD patients. Homocysteine levels were negatively associated with in Mini-Mental State Examination (MMSE) and Neuropsyhcological Test Battery Vienna (NTBV) factors F1-F4 (F1 = attention, F2 = memory, F3 = executive functions, F4 = naming/verbal comprehension). Moreover, higher homocysteine levels significantly predicted shorter five-year survival in the logistic regression models, even after adjusting for age, diagnostic subgroups, sex, years of education and results of neuropsychological testing.

Conclusion: The results of this study suggest that homocysteine levels are independently associated with impaired cognitive function and increased five-year mortality.