Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.
BACKGROUND
The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood.


OBJECTIVE
We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior.


METHODS
Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants.


RESULTS
Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers.


CONCLUSIONS
The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.
['Ingber|Adam P|AP|', 'Hassenstab|Jason|J|', 'Fagan|Anne M|AM|', 'Benzinger|Tammie L S|TL|', 'Grant|Elizabeth A|EA|', 'Holtzman|David M|DM|', 'Morris|John C|JC|', 'Roe|Catherine M|CM|']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D001921:Brain D058245:Cognitive Reserve D015331:Cohort Studies D003863:Depression D005260:Female D015577:Geriatric Assessment D006801:Humans D007091:Image Processing, Computer-Assisted D016014:Linear Models D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D009483:Neuropsychological Tests D011569:Psychiatric Status Rating Scales D011795:Surveys and Questionnaires D016875:tau Proteins
biomarkers dementia cognitive reserve Alzheimer’s disease