Biomarkers and Functional Decline in Prodromal Alzheimer’s Disease

Abstract

BACKGROUND:Little is known of possible associations between Alzheimer's disease (AD) biomarkers and instrumental activities of daily living (IADL) change over time. OBJECTIVE:The present study seeks to identify relationships between baseline imaging and fluid biomarker profiles, and decline in IADL utilising data collated from the AD Neuroimaging Initiative (ADNI) cohort. METHODS:Generalised estimating equations analysis, adjusted for cognitive deterioration, was applied to a cohort of 509 individuals from all stages of ADNI, including 156 healthy controls, 189 early mild cognitive impairment (MCI) patients and 164 MCI patients. RESULTS:A significant correlation was found between baseline biomarkers -specifically CSF Aβ and FDG PET, and IADL change over a 3-year period in individuals with MCI. Importantly, comparable correlations between presence of pathological biomarker levels and temporal decline in both functional and cognitive performance were also noted. DISCUSSION:We show that distinct baseline biomarkers may predict latent changes in IADL.Our results necessitate a revision of the commonly held view upholding cognitive changes as the predominant endpoint measure associated with presence of abnormal baseline biomarkers.

FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort

“…First, these findings are consistent with the current literature on AD diagnostic strategies, that shows higher accuracy for FDG-PET as compared to other biomarkers ( Bloudek et al, 2011 ; Dukart et al, 2015 ; Fellgiebel et al, 2007 ; Iaccarino et al, 2017 ; Landau et al, 2010 ; Perani et al, 2016 ; Robb et al, 2017 ; Shaffer et al, 2013 ; Yuan et al, 2009 ). Of note, a recent study on the prognostic value of the NIA-AA ( McKhann et al, 2011b ), IWG-2 and IWG-1 criteria ( Dubois et al, 2007 , Dubois et al, 2014 ), showed that classification based on the NIA-AA criteria for AD dementia diagnosis, in which amyloid PET and FDG-PET biomarkers are considered, reached the highest prediction accuracy in a clinical setting ( Vos et al, 2015 ).…”

“…To overcome this limit, diagnostic biomarkers such as neuroimaging (i.e., MRI, FDG-PET and amyloid-PET) and cerebrospinal fluid-CSF (i.e., Aβ42, total (t-Tau) and phosphorylated (p-Tau) Tau measures) have been included in the current research criteria for “MCI due to AD” ( Albert et al, 2011 ). Among these biomarkers, the FDG-PET patterns of hypometabolism seem to be particularly accurate in predicting conversion from MCI to dementia, when compared to other biomarkers ( Anchisi et al, 2005 ; Bloudek et al, 2011 ; Dukart et al, 2015 ; Fellgiebel et al, 2007 ; Landau et al, 2010 ; Perani et al, 2016 ; Prestia et al, 2013a ; Robb et al, 2017 ; Shaffer et al, 2013 ; Yuan et al, 2009 ). Notably, a recent meta-analysis on a large sample of MCI (N = 97) has shown that adding FDG-PET imaging information to clinical data provides a better prediction of conversion from MCI to dementia in comparison with clinical data alone, with misclassification rate dropping from 41.3% (clinical data alone) to 27.2% (combined clinical and FDG-PET data) ( Shaffer et al, 2013 ).…”

Characterizing biomarker features of cognitively normal individuals with ventriculomegaly

“…However, there was no significant difference in [ 18 F]FDG SUVR in temporal gyrus between the two groups. It has been reported that medial temporal regions were also often affected in AD [47] . The decreased [ 18 F]FDG uptake in both the angular and posterior cingulate regions, not in the temporal area, in the group with ventriculomegaly made this biomarker profile look unlike typical AD.…”

Validation of the Cognitive Telephone Screening Instruments COGTEL and COGTEL+ in Identifying Clinically Diagnosed Neurocognitive Disorder Due to Alzheimer’s Disease in a Naturalistic Clinical Setting

“…The diagnosis of MiND and MaND due to AD was based on the DSM-5 diagnostic criteria [20] and on the diagnostic guidelines of the National Institute on Aging-Alzheimer Association [5,6]. In individuals without cognitive impairment, neither cognitive deficits nor functional impairment were detected [21,22]. The clinician who established the diagnoses was blind to the individual performance on COGTEL, COGTEL+ and 3MS.…”