Association between skin autofluorescence–measured advanced glycation end products and cognitive function profile in patients with mild cognitive impairment due to Alzheimer's disease
Saki Tasaka, Masahiro Nakamori, Ryo Shimomura, Teppei Kamimura, Tatsuya Otani, Megumi Toko, Tomohisa Nezu, Yu Yamazaki, Shinichi Wakabayashi, Hirofumi MaruyamaBackground
Advanced glycation end products (AGEs) are associated with lifestyle-related diseases, atherosclerosis, and cognitive decline. However, whether AGE accumulation contributes to cognitive dysfunction independently of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) remains unclear.
Objective
To investigate the association of AGE accumulation, measured by skin autofluorescence, with cognitive function, neuroimaging findings, and cerebrospinal fluid (CSF) Aβ 42/40 ratio in patients with mild cognitive impairment (MCI) due to AD.
Methods
Patients with MCI due to AD, defined by a reduced CSF Aβ
42/40
ratio, were enrolled. AGE accumulation was assessed by skin autofluorescence using the AGE Reader
®
. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Brain magnetic resonance imaging findings and CSF biomarkers were analyzed. Associations between AGE levels and clinical variables were assessed by univariate analyses, and variables with
Results
Thirty-one patients (mean age, 74.0 ± 8.5 years; 12 men) were included. In univariate analyses, lower MMSE scores were associated with higher HbA1c levels, whereas lower FAB scores were associated with older age, higher HbA1c, greater medial temporal atrophy, higher Fazekas scores, and greater AGE accumulation. In multivariate analyses, AGE accumulation was independently associated with lower FAB scores. No significant association was observed between AGE accumulation and MMSE scores or the CSF Aβ 42/40 ratio.
Conclusions
AGE accumulation was independently associated with frontal lobe dysfunction, but not amyloid pathology, in patients with MCI due to AD, suggesting that AGEs may contribute to cognitive dysfunction through amyloid-independent pathways.