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Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease

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Abstract

Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.

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Acknowledgments

This work was supported by grant #R01AG034499-03 and a VA Merit Review (S. J. Karve, A. Lee, K. O. Juarez, and M.F. Mendez), Alzheimer’s Disease Research Center Grant NIA P50 AG-16570 (M.F. Mendez, J.M. Ringman). Dr. Ringman receives additional support from PHS K08 AG-22228, California DHS #04-35522, California Alzheimer’s Disease Center Grant 09-11408, and the Easton Consortium for Alzheimer’s Disease Drug Discovery and Biomarkers.

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Authors and Affiliations

  1. Department of Neurology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, USA

    Simantini J. Karve, John M. Ringman & Mario F. Mendez

  2. Section of Neurology, Neurobehavior Unit (691/116AF), V.A. Greater Los Angeles Healthcare Center, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA

    Simantini J. Karve, Kevin O. Juarez & Mario F. Mendez

  3. Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, USA

    John M. Ringman & Mario F. Mendez

  4. Mary S. Easton Center for Alzheimer’s Disease Research, University of California at Los Angeles, Los Angeles, USA

    John M. Ringman & Mario F. Mendez

  5. Western University of Health Sciences, Pomona, USA

    Albert S. Lee & Mario F. Mendez

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  1. Simantini J. Karve
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Correspondence to Simantini J. Karve.

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Karve, S.J., Ringman, J.M., Lee, A.S. et al. Comparison of clinical characteristics between familial and non-familial early onset Alzheimer’s disease. J Neurol 259, 2182–2188 (2012). https://doi.org/10.1007/s00415-012-6481-y

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  • DOI: https://doi.org/10.1007/s00415-012-6481-y

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