Objective To investigate the diagnostic value of plasma amyloid β-protein 40（ Aβ40）， Aβ42 and phosphorylated tau protein（ p-tau） in the diagnosis of senile generalized brain atrophy（ GBA） and their correlation with cognitive function. Methods A total of 125 elderly GBA patients admitted to the Department of Neurology of Hubei Jingmen No. 2 People's Hospital， from May 2018 to January 2019， were retrospectively selected. The subjects were divided into GBA-CFI group with 57 cases and GBA-NCFI group with 68 cases according to whether combined with cognitive dysfunction（ CFI）. Another 130 healthy subjects were selected as the control group. The plasma Aβ40， Aβ42 and p-tau levels of all subjects were measured. According to the Mini Mental State Examination（ MMSE） scale， the GBA-CFI group was classified as the severe CFI group（ ≤9 points， n=14）， moderate CFI group（ 10～20 points， n=19） and mild CFI group（ ≥21 points， n=24）. The relationship between plasma Aβ40， Aβ42， p-tau levels and CFI in elderly patients with GBA and the diagnostic value of CFI in elderly patients with GBA was analyzed. Pearson correlation analysis was used to analyze the correlation between Aβ40， Aβ42 and p-tau levels. Multivariate logistic regression analysis was used to analyze the influencing factors of CFI in elderly patients with GBA. Receiver operating characteristic （ROC） curve was used to analyze the diagnostic value of Aβ40， Aβ42 and p-tau levels in elderly GBA with CFI. Results The levels of plasma Aβ40， Aβ42， and p-tau in the GBA-CFI group were significantly higher than those in the GBA-NCFI group and control group， and the levels of plasma Aβ40， Aβ42， and p-tau in the GBANCFI group were significantly higher than those in the control group. The levels of Aβ40， Aβ42， and p-tau of the GAB-CFI group， GBA-NCFI group and the control group was（ 910.33±275.76）μg/L vs（ 798.28±272.73） vs （667.10±240.63）μg/L，（ 89.81±18.32）μg/L vs（ 69.39±14.39） vs（ 47.84±14.88）μg/L，（ 80.21±18.89）ng/L vs（ 58.84±16.20） vs（ 21.52±10.53）ng/L， respectively（ all P ＜0.05）. The levels of plasma Aβ40， Aβ42， and p-tau of patients in the GBA-CFI group increased with the aggravation of CFI. The levels of plasma Aβ40， Aβ42， and p-tau of the severe， moderate and mild CFI group were（ 1134.21±162.20），（ 950.97±247.72）， （747.56±250.47）μg/L；（ 107.71±8.92），（ 95.79±12.28），（ 74.62±13.73）μg/L；（ 104.71±8.21）， （84.52±5.07），（ 62.51±10.14）（ all P＜0.05）. Pearson correlation analysis showed that plasma Aβ40， Aβ42 were positively correlated with p-tau levels in the GBA-CFI group（ r=0.715， 0.655， all P＜0.05）. Multivariate logistic regression analysis showed that Aβ40 （OR=1.653， 95%CI： 1.186-2.302）， Aβ42 （OR=1.064， 95%CI： 1.027-1.103）， p-tau（ OR=1.080， 95%CI： 1.040-1.121） are risk factors for CFI in elderly GBA patients（ all P＜ 0.05）. ROC curve analysis showed that the area under the curve（ AUC） of plasma Aβ40+Aβ42+p-tau level in the diagnosis of elderly GBA was significantly larger than that of Aβ40， Aβ42， and p-tau respectively（ all P＜0.05）， and the sensitivity， specificity and accuracy were also higher than those of Aβ40， Aβ42， and p-tau respectively. Conclusions The levels of plasma Aβ40， Aβ42 and p-tau in elderly GBA patients are significantly increased， which are closely related to the occurrence of CFI. Combined detection can improve the diagnostic value of elderly GBA.