Table 2.

Effects of Cerebrolysin®, donepezil, and combination therapy on plasma neuronal-derived extracellular vesicles (NDEV) biomarkers in AD: Baseline clinical data and week 28 results

	Cerebrolysin®	Donepezil	Combination	Analysis
	(n = 38)	(N = 36)	(n = 36)
	N (%)	N (%)	N (%)	χ2	df	p
Females	31 (81.6)	28 (77.8)	31 (86.1)	0.843	2	0.656
APOE ɛ4 allele	19 (50.9)	15 (41.7)	15 (41.7)	0.699	2	0.705
	Mean±SD	Mean±SD	Mean±SD	F	df	p
Age (y)	75.44±6.21	76.08±7.87	72.52±8.12	2.355	2, 107	0.100
MMSE (score)	17.26±4.62	17.69±4.52	17.63±5.03	0.092	2, 107	0.913
ADAS-Cog+(score)	41.38±16.11	40.80±17.56	40.73±19.75	0.015	2, 107	0.985
Plasma NDE levels (nL)	Mean ± SD			F	df	p
Baseline Aβ42	1.74±1.36	1.87±1.63	1.68±1.21	0.170	2	0.844
Week-28 Aβ42	1.65±1.36	1.74±1.53	1.08±1.54	2.040	2	0.135
Baseline Total-tau	4.12±0.93	4.21±0.97	4.18±1.18	0.077	2	0.926
Week-28 Total-tau	4.01±0.95	4.51±0.92	4.06±1.01	2.824	2	0.064
Baseline P-T181-tau	3.41±0.97	3.63±0.80	3.30±0.85	1.307	2	0.275
Week-28 P-T181-tau	3.26±0.82*	3.73±0.66	3.23±0.78*	4.900	2	0.009
Baseline P-S396-tau	2.83±0.87	3.03±1.02	2.92±0.86	0.444	2	0.643
Week-28 P-S396-tau	2.75±0.85	3.13±0.98	2.65±0.86	2.770	2	0.067
Baseline NRGN	5.09±1.05	5.20±0.90	4.92±0.75	0.811	2	0.447
Week-28 NRGN	4.79±1.26	5.14±1.13	4.67±1.35	1.340	2	0.266
Baseline REST	5.74±0.91	5.78±1.06	5.45±0.68	1.476	2	0.233
Week-28 REST	5.71±0.88	5.73±0.78	5.40±0.91	1.597	2	0.207

Aβ₄₂, amyloid-β 1-42; ADAS-cog+, AD assessment scale-cognitive subscale modified; MMSE, Mini-Mental State Examination; nL, natural log; NRGN, Neurogranin; P-T181-tau, tau phosphorylated at threonine 181; P-S396-tau, tau phosphorylated at serine 396; REST, repressor element 1-silencing transcription factor. Chi-Square (χ²) and ANOVA (F) analyses were employed. *p < 0.05 versus donepezil group (ANOVA).