Comparative evaluation of clinical and cerebrospinal fluid biomarker characteristics in rapidly and non-rapidly progressive Alzheimer's disease (vol 15, 106, 2023)

被引:1
作者
Herden, Janne Marieke [1 ,2 ]
Hermann, Peter [1 ,2 ]
Schmidt, Isabel [1 ,2 ]
Dittmar, Kathrin [1 ,2 ]
Canaslan, Sezgi [1 ,2 ]
Weglage, Luise [1 ,2 ]
Nuhn, Sabine [1 ,2 ]
Volpers, Corinna [1 ,2 ]
Schlung, Astrid [1 ,2 ]
Goebel, Stefan [1 ,2 ,3 ]
Kueck, Fabian [4 ]
Villar-Pique, Anna [1 ,2 ]
Schmidt, Christian [1 ,2 ,5 ]
Wedekind, Dirk [6 ]
Zerr, Inga [1 ,2 ,3 ]
机构
[1] Univ Med Ctr, Clin Dementia Ctr, Dept Neurol, Robert Koch Str 40, D-37075 Gottingen, Germany
[2] Univ Med Ctr, Natl Reference Ctr CJD Surveillance, Robert Koch Str 40, D-37075 Gottingen, Germany
[3] German Ctr Neurodegenerat Dis DZNE, Gottingen, Germany
[4] Univ Med Ctr Gottingen, Dept Med Stat, Humboldtallee 32, D-37073 Gottingen, Germany
[5] Neurol Gemeinschaftspraxis Groner Tor, Gottingen, Germany
[6] Univ Med Ctr, Dept Psychiat & Psychotherapy, Von Siebold Str 5, D-37075 Gottingen, Germany
关键词
Alzheimer’s disease; APOE; Biomarkers; Phenotype; Rapidly progressive Alzheimer’s disease;
D O I
10.1186/s13195-023-01263-0
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Rapidly progressive forms of Alzheimer’s disease (rpAD) are increasingly recognized and may have a prevalence of up to 30% of patients among all patients with Alzheimer’s disease (AD). However, insights about risk factors, underlying pathophysiological processes, and clinical characteristics of rpAD remain controversial. This study aimed to gain a comprehensive picture of rpAD and new insights into the clinical manifestation to enable a better interpretation of disease courses in clinical practice as well as in future clinical studies. Methods: Patients (n = 228) from a prospective observational study on AD were selected and categorized into rpAD (n = 67) and non-rpAD (n = 161) disease groups. Patients were recruited through the German Creutzfeldt-Jakob disease surveillance center and the memory outpatient clinic of the Göttingen University Medical Center, representing diverse phenotypes of the AD population. Biomarkers and clinical presentation were assessed using standardized protocols. A drop of ≥ MMSE 6 points within 12 months defined rapid progressors. Results: Lower CSF Amyloid beta 1–42 concentrations (p = 0.048), lower Amyloid beta 42/40 ratio (p = 0.038), and higher Tau/Amyloid-beta 1–42 ratio, as well as pTau/Amyloid-beta 1–42 ratio (each p = 0.004) were associated with rpAD. Analyzes in a subset of the cohort (rpAD: n = 12; non-rpAD: n = 31) showed higher CSF NfL levels in rpAD (p = 0.024). Clinically, rpAD showed earlier impairment of functional abilities (p < 0.001) and higher scores on the Unified Parkinson’s Disease Rating Scale III (p < 0.001), indicating pronounced extrapyramidal motor symptoms. Furthermore, cognitive profiles (adjusted for overall cognitive performance) indicated marked deficits in semantic (p = 0.008) and phonematic (0.023) verbal fluency tests as well as word list learning (p = 0.007) in rpAD compared to non-rpAD. The distribution of APOE genotypes did not differ significantly between groups. Conclusions: Our results suggest that rpAD is associated with distinct cognitive profiles, earlier occurrence of non-cognitive symptoms, extrapyramidal motoric disturbance, and lower Amyloid-beta 1–42 concentrations in the CSF. The findings may help to characterize a distinct phenotype of rpAD and estimate prognosis based on clinical characteristics and biomarker results. However, an important future goal should be a unified definition for rpAD to enable targeted study designs and better comparability of the results. © 2023, The Author(s).
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  • [1] Herden JM, 2023, ALZHEIMERS RES THER, V15, DOI 10.1186/s13195-023-01249-y