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INTRODUCTION: Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage. METHODS: A sample of 210 adults (aged 40-59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. Apolipoprotein E (apoE) status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated. RESULTS: Lower hippocampal volumes (P = .04) were associated with poorer spatial location recall and higher Dementia Risk Scores with poorer visual recognition (P = .0005), and lower brain and hippocampal volume (P < .0001, P = .04, respectively). Family history subgroup participants closer to dementia onset had lower scores on visual working memory (P = .05), whereas those with an APOE ε4 allele performed better on form perception (P = .005). DISCUSSION: Middle-aged adults at risk of dementia show evidence of poorer cognitive performance, principally in visuospatial functions.

Original publication




Journal article


Alzheimers Dement

Publication Date





1089 - 1097


Alzheimer's disease, Cognition, Diagnosis, MRI, Neuropsychology, Preclinical, Prognosis, Adult, Alzheimer Disease, Apolipoprotein E4, Cognition Disorders, Female, Genotype, Hippocampus, Humans, Imaging, Three-Dimensional, Logistic Models, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Parents, Psychiatric Status Rating Scales