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Linda Ercoli, PhD; Prabha Siddarth, PhD; Sung-Cheng Huang, PhD; Karen Miller, PhD; Susan Y. Bookheimer, PhD; Benjamin C. Wright, MD; Michael E. Phelps, PhD; Gary Small, MD

Arch Gen Psychiatry. 2006;63:442-448.

Context  Concerns about age-related memory loss are greater in persons who have the apolipoprotein E-IV (APOE4) genetic risk for Alzheimer disease, but the correlation between the degree of concerns and future cerebral metabolic decline is unknown.

Objective  To investigate whether the degree of self-perceived memory loss is associated with regional cerebral metabolic decline.

Design  Longitudinal study.

Setting  Aging and Memory Research Center, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles.

Participants  Thirty right-handed, cognitively intact, middle-aged and older adults (age range, 50-82 years) with age-associated memory complaints, 14 of whom were carriers of the apolipoprotein E-IV allele, were recruited for longitudinal study.

Main Outcome Measures  At baseline, we administered a standardized neuropsychological battery and assessed self-appraisal of memory functioning using the Memory Functioning Questionnaire, which yields 4 factor scores indicating frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics use. Regional cerebral glucose metabolism was determined using fluorodeoxyglucose F18–positron emission tomography at baseline and after 2 years.

Results  At baseline, APOE4 carriers and noncarriers did not differ significantly on objective memory measures or on Memory Functioning Questionnaire factor scores. However, the factor score for frequency of forgetting significantly correlated with global cerebral metabolic decline in all subjects regardless of APOE4 genetic risk (P = .01). By contrast, the factor score for mnemonics use significantly correlated with metabolic decline in the temporal regions in APOE4 carriers but not in noncarriers (P = .03).

Conclusions  The degree of perceived memory loss correlates with subsequent global cerebral metabolic decline for APOE4 carriers and noncarriers; hence, memory complaints may reflect underlying cerebral metabolic changes. Compensatory strategies, as reflected by more frequent mnemonics use in APOE4 carriers, may reflect underlying metabolic changes in the brain regions associated with prodromal Alzheimer disease. Self-reported mnemonics use may be helpful in identifying persons for clinical monitoring.

Author Affiliations: Departments of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior (Drs Ercoli, Siddarth, Miller, Bookheimer, Wright, and Small), and Molecular and Medical Pharmacology, David Geffen School of Medicine (Drs Huang and Phelps), and Center on Aging (Dr Small), University of California, Los Angeles.

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