Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 12
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Hagen, Katja Ehlis, Ann-Christine Haeussinger, Florian B. Beeretz, Stefan Kromer, Gina V. Heinzel, Sebastian Maetzler, Walter Eschweiler, Gerhard W. Berg, Daniela Fallgatter, Andreas J. and Metzger, Florian G. 2015. The relation of SMI and the VSEP in a risk sample for neurodegenerative disorders. Journal of Neural Transmission, Vol. 122, Issue. 8, p. 1167.

    Lista, Simone Molinuevo, Jose L. Cavedo, Enrica Rami, Lorena Amouyel, Philippe Teipel, Stefan J. Garaci, Francesco Toschi, Nicola Habert, Marie-Odile Blennow, Kaj Zetterberg, Henrik O’Bryant, Sid E. Johnson, Leigh Galluzzi, Samantha Bokde, Arun L.W. Broich, Karl Herholz, Karl Bakardjian, Hovagim Dubois, Bruno Jessen, Frank Carrillo, Maria C. Aisen, Paul S. Hampel, Harald Tales, Andrea Jessen, Frank Butler, Christopher Wilcock, Gordon Phillips, Judith and Bayer, Tony 2015. Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline. Journal of Alzheimer's Disease, Vol. 48, Issue. s1, p. S171.

    Risacher, Shannon L. Kim, Sungeun Nho, Kwangsik Foroud, Tatiana Shen, Li Petersen, Ronald C. Jack, Clifford R. Beckett, Laurel A. Aisen, Paul S. Koeppe, Robert A. Jagust, William J. Shaw, Leslie M. Trojanowski, John Q. Weiner, Michael W. and Saykin, Andrew J. 2015. APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. Alzheimer's & Dementia, Vol. 11, Issue. 12, p. 1417.

    Sun, Yu Yang, Fu-Chi Lin, Ching-Po and Han, Ying 2015. Biochemical and Neuroimaging Studies in Subjective Cognitive Decline: Progress and Perspectives. CNS Neuroscience & Therapeutics, Vol. 21, Issue. 10, p. 768.

    Campos-Magdaleno, María Facal, David Juncos-Rabadán, Onésimo Braña, Teresa and Pereiro, Arturo Xosé 2014. Cluster subtypes of the Spanish version of the California Verbal Learning Test in a sample of adults with subjective memory complaints. Journal of Clinical and Experimental Neuropsychology, Vol. 36, Issue. 3, p. 317.

    DiBattista, Amanda Marie Stevens, Benson W. Rebeck, G. William and Green, Adam E. 2014. Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults. Frontiers in Human Neuroscience, Vol. 8,

    Fouquet, Marine Besson, Florent L. Gonneaud, Julie La Joie, Renaud and Chételat, Gaël 2014. Imaging Brain Effects of APOE4 in Cognitively Normal Individuals Across the Lifespan. Neuropsychology Review, Vol. 24, Issue. 3, p. 290.

    Jessen, Frank Amariglio, Rebecca E. van Boxtel, Martin Breteler, Monique Ceccaldi, Mathieu Chételat, Gaël Dubois, Bruno Dufouil, Carole Ellis, Kathryn A. van der Flier, Wiesje M. Glodzik, Lidia van Harten, Argonde C. de Leon, Mony J. McHugh, Pauline Mielke, Michelle M. Molinuevo, Jose Luis Mosconi, Lisa Osorio, Ricardo S. Perrotin, Audrey Petersen, Ronald C. Rabin, Laura A. Rami, Lorena Reisberg, Barry Rentz, Dorene M. Sachdev, Perminder S. de la Sayette, Vincent Saykin, Andrew J. Scheltens, Philip Shulman, Melanie B. Slavin, Melissa J. Sperling, Reisa A. Stewart, Robert Uspenskaya, Olga Vellas, Bruno Visser, Pieter Jelle and Wagner, Michael 2014. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimer's & Dementia, Vol. 10, Issue. 6, p. 844.

    Samieri, Cécilia Proust-Lima, Cécile M. Glymour, Maria Okereke, Olivia I. Amariglio, Rebecca E. Sperling, Reisa A. Rentz, Dorene M. and Grodstein, Francine 2014. Subjective cognitive concerns, episodic memory, and the APOE ε4 allele. Alzheimer's & Dementia, Vol. 10, Issue. 6, p. 752.

    Singer, Joel Trollor, Julian N. Baune, Bernhard T. Sachdev, Perminder S. and Smith, Evelyn 2014. Arterial stiffness, the brain and cognition: A systematic review. Ageing Research Reviews, Vol. 15, p. 16.

    Bender, Andrew R. and Raz, Naftali 2012. Age-related differences in memory and executive functions in healthy APOE ɛ4 carriers: The contribution of individual differences in prefrontal volumes and systolic blood pressure. Neuropsychologia, Vol. 50, Issue. 5, p. 704.

    Eramudugolla, Ranmalee Cherbuin, Nicolas Easteal, Simon Jorm, Anthony F. and Anstey, Kaarin J. 2012. Self-Reported Cognitive Decline on the Informant Questionnaire on Cognitive Decline in the Elderly Is Associated with Dementia, Instrumental Activities of Daily Living and Depression but Not Longitudinal Cognitive Change. Dementia and Geriatric Cognitive Disorders, Vol. 34, Issue. 5-6, p. 282.


Interaction effects of subjective memory impairment and ApoE4 genotype on episodic memory and hippocampal volume

  • N. Striepens (a1), L. Scheef (a2), A. Wind (a1), D. Meiberth (a1), J. Popp (a1), A. Spottke (a1) (a3), H. Kölsch (a1), M. Wagner (a1) and F. Jessen (a1)
  • DOI:
  • Published online: 02 February 2011

The apolipoprotein E4 allele (ApoE4) is an established genetic risk factor for Alzheimer's disease (AD). However, its effects on cognitive performance and brain structure in healthy individuals are complex. We investigated the effect of ApoE4 on cognitive performance and medial temporal lobe volumetric measures in cognitively unimpaired young elderly with and without subjective memory impairment (SMI), which is an at-risk condition for dementia.


Altogether, 40 individuals with SMI and 62 without were tested on episodic memory and on tasks of speed and executive function. All participants were ApoE genotyped. 21 subjects with SMI and 47 without received additional structural magnetic resonance imaging. Volumetric measures of the hippocampus, the entorhinal cortex and the amygdala were obtained manually.


In the SMI group, ApoE4 carriers performed worse on the episodic memory (p=0.049) and showed smaller left hippocampal volumes (p=0.030). In the individuals without SMI, the ApoE4 carriers performed better on episodic memory (p=0.018) and had larger right hippocampal volumes (p=0.039). The interaction of group (SMI/no SMI) and ApoE genotype was significant for episodic memory (p=0.005) and right and left hippocampal volumes (p=0.042; p=0.035). There were no within-group differences or interaction effects on speed and executive function composite measures or other volumetric measures.


The negative effect of ApoE4 on episodic memory and hippocampal volume in SMI supports SMI as a prodromal condition of AD. The positive effects of ApoE4 in subjects without SMI adds to a number of reports on positive ApoE4 effects in young and very old individuals.

Corresponding author
*Address for correspondence: Prof. Dr. med. F. Jessen, Department of Psychiatry, University of Bonn, Bonn, Germany. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

MM Adamson , KM Landy , S Duong , S Fox-Bosetti , JW Ashford , GM Murphy , M Weiner , JL Taylor (2010). Apolipoprotein E4 influences on episodic recall and brain structures in aging pilots. Neurobiology of Aging 31, 10591063.

F Agosta , KA Vossel , BL Miller , R Migliaccion , SJ Bonasera , M Filippi , AL Boxer , A Karydas , KL Possin , ML Gorno-Tempini (2009). Apolipoprotein E4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia. Proceedings of the National Academy of Sciences USA 106, 20182022.

DA Bennett , JA Schneider , RS Wilson , JL Bienias , E Berry-Kravis , SE Arnold (2005). Amyloid mediates the association of apolipoprotein E4 allele to cognitive function in older people. Journal of Neurology, Neurosurgery and Psychiatry 76, 11941199.

M Boccardi , F Sabattoli , C Testa , A Beltramello , H Soininen , GB Frisoni (2004). APOE and modulation of Alzheimer's and frontotemporal dementia. Neuroscience Letters 356, 167170.

G Bu (2009). Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nature Reviews Neuroscience 10, 333344.

DB Carr , J Gray , JC Morris (2000). The value of informant versus individual's complaints of memory impairment in early dementia. Neurology 55, 17241726.

N Cherbuin , LS Leach , H Christensen , KJ Anstey (2007). Neuroimaging and APOE genotype: a systematic qualitative review. Dementia and Other Geriatric Cognitive Disorders 24, 348362.

S Cosentino , N Scarmeas , E Helzner , MM Glymour , J Brandt , M Albert , D Blacker , Y Stern (2008). ApoE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease. Neurology 70, 18421849.

MR Farlow , Y He , S Tekin , J Xu , R Lane , HC Charles (2004). Impact of ApoE in mild cognitive impairment. Neurology 63, 18981901.

A Fleisher , M Grundman , CR Jack Jr., RC Petersen , C Taylor , HT Kim , DH Schiller , V Bagwell , D Sencakova , MF Weiner , C DeCarli , ST DeKosky , CH van Dyck , LJ Thal (2005). Sex apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment. Archives of Neurology 62, 953957.

I Goncharova , BC Dickerson , TR Stoub , L deToledo-Morell (2001). MRI of human entorhinal cortex: a reliable protocol for volumetric measurement. Neurobiology of Aging 22, 737745.

DG Harwood , WW Barker , RL Ownby , M Mullan , R Duara (2004). No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly. International Journal of Geriatric Psychiatry 19, 11311139.

F Jessen , L Feyen , K Freymann , R Tepest , W Maier , R Heun , HH Schild , L Scheef (2006). Volume reduction of the entorhinal cortex in subjective memory impairment. Neurobiology of Aging 27, 17511756.

F Jessen , B Wiese , C Bachmann , S Eifflaender-Gorfer , F Haller , H Kölsch , T Luck , E Mösch , H van den Bussche , M Wagner , A Wollny , T Zimmermann , M Pentzek , SG Riedel-Heller , HP Romberg , S Weyerer , H Kaduszkiewicz , W Maier , H Bickel , Cognition and Dementia in Primary Care Patients Study Group (2010). Prediction of dementia by subjective memory impairment: effects of severity and temporal association with cognitive impairment. Archives of General Psychiatry 67, 414422.

F Jessen , B Wiese , G Cvetanovska , A Fuchs , H Kaduszkiewicz , H Kölsch , T Luck , E Mösch , M Pentzek , SG Riedel-Heller , J Werle , S Weyerer , T Zimmermann , W Maier , H Bickel (2007). Patterns of subjective memory impairment in the elderly: association with memory performance. Psychological Medicine 37, 17531762.

C Jonker , MI Geerlings , B Schmand (2000). Are memory complaints predictive for dementia? A review of clinical and population-based studies. International Journal of Geriatric Psychiatry 15, 983991.

E Kok , S Haikonen , T Luoto , H Huhtala , S Goebeler , H Haapasalo , PJ Karhunen (2009). Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Annals of Neurology 65, 650657.

J Kornhuber , K Schmidtke , L Frölich , R Perneczky , S Wolf , H Hampel , F Jessen , I Heuser , O Peters , M Weih , H Jahn , C Luckhaus , M Hüll , HJ Gertz , J Schörder , J Pantel , O Rienhoff , SA Seuchter , E Rüther , F Henn , W Maier , J Wiltfang (2009). Early and differential diagnosis of dementia and mild cognitive impairment. Dementia and Other Geriatric Cognitive Disorders 27, 404417.

SM Laws , RM Clarnette , K Taddei , G Martins , A Paton , J Hallmayer , OP Almeida , DM Groth , SE Gandy , H Förstl , RN Martins (2002). APOE-epsilon4 and APOE-491A polymorphisms in individuals with subjective memory loss. Molecular Psychiatry 7, 768775.

H Lemaitre , F Crivello , C Dufouil , B Grassiot , C Tzourio , A Alperovitch , B Mazoyer (2005). No epsilon-4 gene dose effect on hippocampal atrophy in a large MRI database of healthy elderly subjects. Neuroimage 24, 12051213.

J Lind , A Larson , J Petersson , M Ingvar , LG Nilson , L Backma , R Adolfsson , M Cruts , K Sieeers , C van Broeckhoven , L Nyberg (2006). Reduced hippocampal volume in non-demented carriers of apolipoprotein epsilon 4: relation to chronic age and recognition memory. Neuroscience Letters 396, 2327.

M Luciano , AJ Gow , MD Taylor , C Hayward , SE Harris , H Campell , DJ Porteous , JM Starr , PM Visscher , IJ Deary (2009). Apolipoprotein E is not related to memory abilities in 70 years of age. Behaviour Genetics 39, 6–14.

CR Mondadori , DJ deQuervain , A Buchmann , H Mustovic , MA Wollmer , CF Schmidt , P Boesiger , C Hock , RM Nitsch , A Papassotiropoulos , K Henke (2007). Better memory and neural efficiency in young ApoE4 carriers. Cerebral Cortex 17, 19341947.

SG Mueller , MW Weiner (2009). Selective effect of age, ApoE4, and Alzheimer's disease on hippocampal subfields. Hippocampus 19, 558564.

H Müller , I Hasse-Sander , R Horn , C Helmstadter , CE Elger (1997). Rey Auditory-Verbal Learning Test: structure of a modified German version. Journal of Clinical Psychology 53, 663671.

RC Petersen (2009). Early diagnosis of Alzheimer's disease: is MCI too late? Current Alzheimer Research 6, 324330.

RC Petersen , R Doody , A Kurz , RC Mohs , JC Morris , PV Rabins , K Ritchie , M Rossor , L Thal , B Winblad (2001 a). Current concepts in mild cognitive impairment. Archives of Neurology 58, 19851992.

RC Petersen , JC Stevens , M Ganguli , EG Tangalos , JL Cummings , ST DeKosky (2001 b). Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56, 11331142.

JC Pruessner , LM Li , W Series , M Pruessner , DL Collins , N Kabani , S Lupien , AC Evans (2000). Volumetry of hippocampus and amygdale with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cerebral Cortex 10, 433442.

B Reisberg , MB Shulman (2009). Commentary on ‘a roadmap for the prevention of dementia II: Leon Thal Symposium 2008’. Subjective cognitive impairment as an antecedent of Alzheimer's dementia policy import. Alzheimer's and Dementia 5, 154156.

B Reisberg , MB Shulman , C Torossian , L Leng , W Zhu (2010). Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimer's and Dementia 6, 1124.

AJ Saykin , HA Wishart , LA Rabin , RB Santulli , LA Flashman , JD West , TL McHugh , AC Mamourian (2006). Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology 67, 835842.

MR Schultz , MJ Lyons , CE Franz , MD Grant , C Boake , KC Jacobson , H Xian , GD Schellenberg , SA Eisen , WS Kremen (2008). Apolipoprotein E genotype and memory in the sixth decade of life. Neurology 70, 17711777.

GE Smith , DL Bohac , SC Waring , E Kokmen , EG Tangalos , RJ Ivnik , RC Petersen (1998). Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects. Neurology 50, 355362.

E Strauss , O Spreen (1990). A comparison of the Rey and Taylor figures. Archives of Clinical Neuropsychology 5, 417420.

N Striepens , L Scheef , A Wind , J Popp , A Spottke , D Cooper-Mahkorn , H Suliman , M Wagner , HH Schild , F Jessen (2010). Volume loss of the medial temporal lobe structures in subjective memory impairment. Dementia and Other Cognitive Disorders 29, 7581.

LA Tupler , KR Krishnan , DL Greenberg , SM Marcovina , ME Payne , JR Macfall , HC Charles , PM Doraiswamy (2006). Predicting memory decline in normal elderly: genetics, MRI and cognitive reserve. Neurobiology of Aging 28, 16441656.

WM van der Flier , AE van der Vlies , AW Weverling-Rijnsburger , NL de Boer , F Admiraal-Behloul , EL Bollern , RG Westendorp , MA van Buchem , HA Middelkoop (2005). MRI measures and progression of cognitive decline in non-demented elderly attending a memory clinic. International Journal of Geriatric Psychiatry 20, 10601066.

P-N Wang , H-C Liu , J-F Ling , K-N Lin , Z-A Wu (2009). Accelerated hippocampal atrophy rates in stable and progressive amnestic mild cognitive impairment. Psychiatry Research 171, 221231.

B Winblad , K Palmer , M Kivipelto , V Jelic , L Fratiglioni , LO Wahlund , A Nordberg , L Bäckman , M Albert , O Almkvist , H Arai , H Basun , K Blennow , M deLeon , C DeCarli , T Erkinjuntti , E Giacobini , C Graff , J Hardy , C Jack , A Jorm , K Ritchie , C van Duijn , P Visser , RC Petersen (2004). Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine 256, 240246.

HU Wittchen , S Zhao , JM Abelson , JL Abelson , RC Kessler (1996). Reliability and procedural validity of UM-CIDI SMI-II-R phobic disorders. Psychological Medicine 26, 11691177.

N Zhong , KH Weisgraber (2009). Understanding the basis for the association of apoE4 with Alzheimer's disease: opening the door for therapeutic approaches. Current Alzheimer Research 6, 415418.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *