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Subjective cognitive failures and hippocampal volume in elderly with white matter lesions

From the Department of Neurology (A.G.W.v.N., W.F.F., K.F.d.L., I.W.M.v.U., L.J.B.v.O., F.E.d.L.), Department of Psychiatry (I.T.), Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition, and Behaviour, and FC Donders Centre for Cognitive Neuroimaging (M.P.Z.), Radboud University Nijmegen, The Netherlands.

Address correspondence and reprint requests to Dr de Leeuw, Department of Neurology, Radboud University Nijmegen Medical Centre, Reinier Postlaan 4, PO-box 9101, 6500 HB Nijmegen, The Netherlands H.deLeeuw{at}neuro.umcn.nl

Background: Subjective cognitive failures (SCF) and subjective memory failures (SMF) have been reported to be an early predictor of Alzheimer disease (AD) and have been attributed to white matter lesions (WML). Since AD is characterized by hippocampal degeneration, it is surprising that its relation with hippocampal atrophy has been investigated only sparsely. Previous studies on this are rare, limited in sample size, and did not adjust for WML.

Objective: To determine the relation between SCF and hippocampal volume in strata of objective cognitive performance among elderly without dementia with incidental WML.

Methods: The Radboud University Nijmegen Diffusion tensor and MRI Cohort study is a prospective cohort study among 503 subjects with WML aged between 50 and 85 years. All subjects underwent FLAIR and T1 MRI scanning. The amount of SCF and SMF was rated by the Cognitive Failure Questionnaire. Cognitive function was assessed by a cognitive screening battery. Volumetric measures of hippocampus and WML were manually performed. We assessed the relation between hippocampal volume and SCF and SMF adjusted for age, sex, education, depression, intracranial volume, and WML volume.

Results: Subjects with SCF and SMF had lower hippocampal volumes than those without (p = 0.01 and p = 0.02). This was most noteworthy in subjects with good objective cognitive performance (p_trend = 0.007 and p_trend = 0.03), and not in those with poor objective cognitive performance.

Conclusion: Subjective cognitive failures (SCF) are associated with lower hippocampal volume, even in subjects without objective cognitive impairment and independent of white matter lesions. SCF has a radiologic detectable pathologic-anatomic substrate.

Abbreviations: AD = Alzheimer disease; ANCOVA = analysis of covariance; CES-D = Center of Epidemiologic Studies–Depression Scale; FLAIR = fluid attenuated inversion recovery; GM = gray matter; ICV = intracranial volume; MMSE = Mini-Mental State Examination; RUN DMC = Radboud University Nijmegen Diffusion tensor and MRI Cohort; SCF = subjective cognitive failures; SEF = subjective executive failures; SMF = subjective memory failures; TE = echo time; TI = inversion time; TR = repetition time; WM = white matter; WML = white matter lesions.

Dr. de Leeuw has received a personal clinical fellowship of the Netherlands Organization for Scientific Research (project number: 40-00703-97-07197) and a fellowship of the Dutch Brain foundation (H04-12).

Disclosure: The authors report no disclosures.

Received April 22, 2008. Accepted in final form July 1, 2008.