Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer’s disease and cognitively unimpaired individuals

Translational Neurodegeneration

Nagaendran Kandiah¹  Hui Chiew¹  Kok Pin Ng¹  Zahinoor Ismail²  Pedro Rosa-Neto³  Serge Gauthier³ 

[1] Department of Neurology, National Neuroscience Institute, Singapore, Singapore;Duke-NUS Medical School, Singapore, Singapore;Lee Kong Chian School of Medicine – Imperial College London, Nanyang Technological University, Singapore, Singapore;Hotchkiss Brain Institute and O’Brien Institute for Public Health; Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada;The McGill University Research Centre for Studies in Aging, Montreal, Canada;

关键词: Neuropsychiatric symptoms;    Preclinical Alzheimer’s disease;    Mild behavioral impairment;    Amyloid-β;    Hyperphosphorylated tau;    Neurodegeneration;   

DOI  :  10.1186/s40035-021-00236-3

来源: Springer

【 摘 要 】

The development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-β (Aβ), tau and neurodegeneration in preclinical AD and cognitively-unimpaired individuals in 19 eligible English-language publications (8 cross-sectional studies, 10 longitudinal, 1 both cross-sectional and longitudinal). The cross-sectional studies have consistently shown that NPS, particularly depressive and anxiety symptoms, are associated with higher Aβ. The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time. However, most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology. For the association of NPS and neurodegeneration, two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD, respectively. However, evidence for the association between atrophy and NPS in preclinical AD is less consistent. Therefore, future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N) biomarkers, NPS and cognitive decline, but also to elucidate the contribution of comorbid pathology to preclinical AD.

【 授权许可】

CC BY