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O2‐08‐04: USING THE A/T/N FRAMEWORK TO EXAMINE DRIVING IN PRECLINICAL AD
Author(s) -
Roe Catherine M.,
Babulal Ganesh M.,
Stout Sarah Holtz,
Carr David B.,
Williams Monique M.,
Benzinger Tammie L.S.,
Fagan Anne M.,
Holtzman Dave M.,
Ances Beau M.,
Morris John C.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2684
Subject(s) - clinical dementia rating , pathological , medicine , cognition , cognitive impairment , dementia , oncology , psychology , gerontology , disease , psychiatry
took part in the Alzheimer’s disease Neuroimaging Initiative (ADNI) study from 2004 and had available morning CSF cortisol and CSFAb42 information were retrospectively evaluated. Reserve was modelled as a latent variable calculated as a weighted sum of standardised proxies of brain (indexed by intracranial volume) and cognitive (indexed by premorbid intelligence/ educational/ occupational attainment) reserve via exploratory factor analysis(EFA). Covariate-adjusted Cox regression models tested whether the association between GC/Ab42 and clinical progression within the study period was modified by reserve; after adjusting for age, sex, APOE-genotype status and subclinical depression. Results:Kaplan-Meier (KM) estimates showed that individuals with baseline abnormal Ab and elevated cortisol levels (GC+/Ab+) were at highest risk of progression to Mild-Cognitive-Impairment-due-to-AD (MCI-AD) and AD, compared to other biomarker-defined groups. Significant GC+*Ab+*reserve interaction for clinical progression was noted (HR1⁄40.15, P<0.001), after adjusting for potential confounders; suggesting a moderating effect of the reserve composite on the deleterious association between GC+/Ab+ and the development of clinically overt cognitive decline. Significantly higher risk for transition to clinical AD state was also detected in individuals carrying at least one APOE-ε4 allele (HR1⁄44.30, P<0.001) and high scores on the Geriatric Depression Scale (GDS), the latter suggestive of subclinical depression/low mood (HR1⁄41.78, P<0.001). Conclusions:Cortisol hyper-secretion at the pre-symptomatic stage is predictive of accelerated clinical progression in cognitively intact individuals, in the presence of abnormal CSF-Ab42.We present the first evidence for the moderating effects of reserve indicators in terms of clinical progression for pre-symptomatic individuals with both CSF amyloid abnormalities and a hyper-glucocorticoid profile. We are currently investigating the precise role of hypercortisolemia in AD-symptom development using relevant approaches including Mendelian randomization.