The journal of prevention of Alzheimer's disease · 2026
Baseline MRI markers and clinical outcomes during anti-amyloid β therapy: A real-world study in a Japanese dementia center.
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Kujuro Yuki, Saito Marina, Maruko Manami, Kamiyama Kazuko, Nakano Aya, Qian Emi, Okamura Teppei, Ito Daisuke, Kageyama Toshimi, Sugiyama Ichiro, Ishihara Eriko, Kuwahara Tatsuro, Moritani Kazunori, Katai Hitoshi, Hattori Hidenori
Аннотация
IMPORTANCE: Predictors of decline and of amyloid-related imaging abnormalities (ARIA) during anti-amyloid β therapy in routine care are undefined.
OBJECTIVE: To identify baseline predictors of cognitive, functional, and safety outcomes.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort of 161 consecutive patients initiating anti-amyloid β therapy at a Tokyo dementia center, 2024 to 2026 (lecanemab, 89; donanemab, 72).
EXPOSURES: Lecanemab or donanemab.
MAIN OUTCOMES AND MEASURES: Change in MMSE and CDR-Sum of Boxes (CDR-SB); baseline medial temporal atrophy (VSRAD Z score), amyloid PET burden, and microbleeds; ARIA.
RESULTS: With lecanemab, MMSE and CDR-SB declined significantly at every assessment (CDR-SB +0.79, +1.10, +1.60 at 6, 12, 18 months); memory and orientation declined while language was preserved. Greater baseline medial temporal atrophy was associated with greater 12-month CDR-SB worsening (r = 0.39; P = .01; n = 40); patients in the most severe standard category (Z ≥ 3) worsened by 2.62 versus 0.64 points (adjusted β = +2.18; P < .001). Atrophy was associated with older age (r = 0.19; P = .03) and with baseline memory-related measures - ADAS-Cog score (r = 0.32; P < .001) and the MMSE subdomains of delayed recall (β = -0.25; P = .006) and time orientation (β = -0.30; P = .04) - but not MMSE total score. Amyloid PET burden showed no significant association at most time points. All ARIA events were asymptomatic; ARIA-H occurred in 6 of 25 with microbleeds versus 3 of 136 without (odds ratio, 14.0; P < .001). Donanemab follow-up was 6 months.
CONCLUSIONS AND RELEVANCE: Baseline medial temporal atrophy was associated with functional decline and microbleeds with ARIA-H. Pretreatment MRI may provide prognostic and safety information during anti-amyloid β therapy.
OBJECTIVE: To identify baseline predictors of cognitive, functional, and safety outcomes.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort of 161 consecutive patients initiating anti-amyloid β therapy at a Tokyo dementia center, 2024 to 2026 (lecanemab, 89; donanemab, 72).
EXPOSURES: Lecanemab or donanemab.
MAIN OUTCOMES AND MEASURES: Change in MMSE and CDR-Sum of Boxes (CDR-SB); baseline medial temporal atrophy (VSRAD Z score), amyloid PET burden, and microbleeds; ARIA.
RESULTS: With lecanemab, MMSE and CDR-SB declined significantly at every assessment (CDR-SB +0.79, +1.10, +1.60 at 6, 12, 18 months); memory and orientation declined while language was preserved. Greater baseline medial temporal atrophy was associated with greater 12-month CDR-SB worsening (r = 0.39; P = .01; n = 40); patients in the most severe standard category (Z ≥ 3) worsened by 2.62 versus 0.64 points (adjusted β = +2.18; P < .001). Atrophy was associated with older age (r = 0.19; P = .03) and with baseline memory-related measures - ADAS-Cog score (r = 0.32; P < .001) and the MMSE subdomains of delayed recall (β = -0.25; P = .006) and time orientation (β = -0.30; P = .04) - but not MMSE total score. Amyloid PET burden showed no significant association at most time points. All ARIA events were asymptomatic; ARIA-H occurred in 6 of 25 with microbleeds versus 3 of 136 without (odds ratio, 14.0; P < .001). Donanemab follow-up was 6 months.
CONCLUSIONS AND RELEVANCE: Baseline medial temporal atrophy was associated with functional decline and microbleeds with ARIA-H. Pretreatment MRI may provide prognostic and safety information during anti-amyloid β therapy.