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. 2022;90(2):543-551.
doi: 10.3233/JAD-220448.

Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia

Ashwati Vipin  1   2 , Chen Ling Koh  2 , Benjamin Yi Xin Wong  2 , Fatin Zahra Zailan  1   2 , Jayne Yi Tan  2 , See Ann Soo  1   2 , Vaynii Satish  2 , Dilip Kumar  1   2 , Brian Zhiyang Wang  2 , Adeline Su Lyn Ng  2   3 , Hui Jin Chiew  2 , Kok Pin Ng  1   2   3 , Nagaendran Kandiah  1   2   3
Affiliations

Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia

Ashwati Vipin et al. J Alzheimers Dis. 2022.

Abstract

We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-β1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A- N+ (β = 1.53; p = 0.036; CI 0.15:2.92) and A- N- (β = 4.68; p = 0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A- N+, T- CVD+ patients showed greater MMSE decline compared to T+CVD- patients (β = - 2.37; p = 0.030; CI - 4.41:- 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A- sub-group.

Keywords: ATN profile; Southeast Asian cohort; cognition; longitudinal; young-onset dementia.

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Conflict of interest statement

Authors’ disclosures available online (https://www.j-alz.com/manuscript-disclosures/22-0448r1).

Figures

Fig. 1
Fig. 1
Young-onset amyloid-positive neurodegeneration-positive dementia patients exhibit greater longitudinal decline in MMSE scores compared to young-onset amyloid-negative neurodegeneration-positive and amyloid-negative neurodegeneration-negative dementia patients. Young-onset patients with high amyloid-β burden (A+) and neurodegeneration (N+), that is, high MTA burden, showed steeper decline in MMSE scores over time when compared to their young-onset A–N+ and A–N– counterparts. Baseline age, sex, education years and baseline MMSE were included as covariates. MMSE, Mini-Mental State Examination; A, amyloid-β; N, neurodegeneration; MTA, medial temporal atrophy.
Fig. 2
Fig. 2
Young-onset sporadic dementia with amyloid-β pathology show steepest decline in MMSE scores compared to patients without amyloid-β, phosphorylated tau or cerebrovascular disease pathology. A+ Young-onset dementia patients showed significant decline in MMSE score than their A–T– CVD– counterparts. However, predominant CVD pathology and predominant T pathology did not significantly influence cognitive decline in comparison to normal biomarker A–T– CVD– patients. Baseline age, sex, education years and baseline MMSE were included as covariates. MMSE, Mini-Mental State Examination; A, amyloid-β; CVD, cerebrovascular disease; T, phospho-tau.
See this image and copyright information in PMC

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