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Does executive impairment define a frontal variant of Alzheimer's disease?

Published online by Cambridge University Press:  19 August 2010

Michael Woodward*
Affiliation:
Aged Care Services, Heidelberg Repatriation Hospital, Austin Health, Heidelberg, Victoria, Australia
Henry Brodaty
Affiliation:
Prince of Wales Hospital, Randwick, Sydney, New South Wales, Australia Dementia Collaborative Research Centre, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
Karyn Boundy
Affiliation:
The Queen Elizabeth Hospital, Woodville South, South Australia, Australia
David Ames
Affiliation:
National Ageing Research Institute, Melbourne, Victoria, Australia
Greg Blanch
Affiliation:
Medical Communications, Janssen-Cilag Pty Ltd, Sydney, New South Wales, Australia
Robert Balshaw
Affiliation:
Syreon Corporation, Vancouver, Canada
*
Correspondence should be addressed to: Michael Woodward, Austin Health/University of Melbourne, Heidelberg Repatriation Hospital, Banksia Street, Heidelberg West, VIC 3081, Australia. Phone: +61 394962185; Fax: +61 394962613. Email: [email protected].
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Abstract

Background: People with Alzheimer's disease (AD) who present with prominent frontal features such as a dysexecutive syndrome may be difficult to differentiate clinically from subjects with frontotemporal lobar degeneration (FTLD). This study was performed to improve the differential diagnosis between AD and FTLD and to better characterize the AD subgroup with greater executive dysfunction.

Methods: Using a well-defined prospectively studied cohort of cognitively impaired subjects, which included those with AD and with FTLD, we nominated a frontal variant of AD (FvAD) group as those AD subjects with the lowest quartile of scores on the Frontal Assessment Battery (FAB), indicating greatest executive dysfunction, and compared them with the rest of the AD cases (whom we called the AD group) and those with FTLD across several baseline variables including cognitive, functional and behavioral scales. We also compared the changes from baseline for these three groups at 6 and 12 months. Additionally, we controlled for dementia severity by matching AD and FTLD cases on a functional scale, the SMAF, and repeated the same comparisons with these severity-matched groups.

Results: The 114 FvAD subjects had a mean age of 78.1 years and Mini-mental State Examination (MMSE) scores of 16.6, and the (remaining) AD group had a mean age of 78.4 years and MMSE of 22.4. There were 30 FTLD subjects with a mean age at baseline of 70.9 years and a mean baseline MMSE of 23.4. The FvAD group was significantly more severely impaired than the other two groups on all baseline assessments except the behavioral scale, the Neuropsychiatric Inventory (NPI), where there was insignificantly less impairment than in the FTLD group. In the analysis of subjects matched at baseline for functional impairment, the FvAD and FTLD groups were not significantly different on most assessment scales although on the FAB, clock-drawing and MMSE the FvAD subjects were still significantly more impaired. These two severity-matched groups were also similar in other baseline characteristics except for older age and less psychotropic use in the FvAD group. The severity-matched FvAD group was significantly different from the AD group in almost all assessment scales. All three unmatched and matched groups declined similarly over 12 months.

Conclusions: When groups were not matched for baseline severity, the use of the FAB defined a group of AD subjects with greater executive dysfunction that were distinguished from both the remainder of the AD and FTLD subjects in almost all domains except behavioral disturbance and probably were just more severely affected AD subjects. The FAB is thus more useful as a marker of dementia severity than as a scale to detect a frontal variant of AD or to distinguish AD from FTLD. Controlling for severity, however, did allow the definition of a subgroup of AD subjects that more closely resembled FTLD subjects than the remainder of the AD subjects. It is proposed that subjects with dementia presenting with greater executive impairment but without prominent behavioral symptoms are likely to have AD rather than FTLD, especially if they are quite functionally impaired. With time FTLD subjects develop increasing executive dysfunction and increasingly resemble the more severely affected AD subjects.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2010

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References

American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IVTR). Washington, DC: American Psychiatric Association.Google Scholar
Becker, J. T., Huff, F. J., Nebes, R. D., Holland, A. and Boller, F. (1998). Neuropsychological function in Alzheimer's disease: pattern of impairment and rates of progression. Archives of Neurology, 45, 263268.CrossRefGoogle Scholar
Bédard, M., Molloy, D. W., Squire, L., Dubois, S., Lever, J. A. and O'Donnell, M. (2001). The Zarit Burden Interview: a new short version and screening version. The Gerontologist, 41, 652657.CrossRefGoogle ScholarPubMed
Binetti, G., Magri, E., Padovani, A., Cappa, S. F., Bianchetti, A. and Trabucchi, M. (1996). Executive dysfunction in early Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry, 60, 9193.CrossRefGoogle ScholarPubMed
Braak, H. and Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathologica (Berlin), 82, 239259.CrossRefGoogle ScholarPubMed
Cairns, N. J., Taylor-Reinwald, L., Morris, J. C. and the Alzheimer's Disease Neuroimaging Initiative (2010). Autopsy consent, brain collection, and standardized neuropathologic assessment of the ADNI participants: the essential role of the Neuropathology Core. Alzheimer's and Dementia, 6, 274279.CrossRefGoogle Scholar
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A. and Gorbein, J. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 23082314.CrossRefGoogle ScholarPubMed
Dubois, B., Slachevsky, A., Litvan, I. and Pillon, B. (2000). The FAB: a frontal assessment battery at bedside. Neurology, 55, 16211626.CrossRefGoogle ScholarPubMed
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). “Mini-mental state”: a practical method of grading the cognitive status of patients for the clinician. Journal of Psychiatry Research, 12, 189198.CrossRefGoogle ScholarPubMed
Forman, M. S. et al. (2006). Frontotemporal dementia: clinicopathological correlates. Annals of Neurology, 59, 952962.CrossRefGoogle Scholar
Galton, C. J., Patterson, K., Xuereb, J. H. and Hodges, J. R. (2000). Atypical and typical presentations of Alzheimer's disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain, 123, 484498.CrossRefGoogle ScholarPubMed
Gorno-Tempini, M. L. et al. (2008). The logopenic/phonological variant of primary progressive aphasia. Neurology, 71, 12271234.CrossRefGoogle ScholarPubMed
Grady, C. L. et al. (1998). Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. Journal of Clinical and Experimental Neuropsychology, 19, 576596.Google Scholar
Greene, J. D. W., Patterson, K., Xuereb, J. and Hodges, J. R. (1996). Alzheimer's disease and confluent progressive aphasia. Archives of Neurology, 53, 10721078.CrossRefGoogle Scholar
Hebert, R., Carrier, R. and Bilodeau, A. (1998). The Functional Autonomy Measurement System (SMAF): description and validation of an instrument for the measurement of handicaps. Age and Ageing, 17, 293302.CrossRefGoogle Scholar
Hodges, J. R. et al. (2004). Clincopathological correlates in frontotemporal dementia. Annals of Neurology, 56, 399406.CrossRefGoogle Scholar
Ikeda, M., Ishikawa, T. and Tanabe, H. (2004). Epidemiology of frontotemporal lobar degeneration. Dementia and Geriatric Cognitive Disorders, 17, 265268.CrossRefGoogle ScholarPubMed
Johnson, J. K., Head, E., Kim, R., Stark, A., Arnold, M. D. and Cotman, C. W. (1999). Clinical and pathological evidence for a frontal variant of Alzheimer's disease. Neurology, 56, 12331239.Google Scholar
Kanne, S. M., Balota, D. A., Storandt, M., McKeel, D. W. Jr, and Morris, J. C. (1998). Relating anatomy to function in Alzheimer's disease: neuropsychological profiles predict regional neuropathology 5 years later. Neurology, 50, 979985.CrossRefGoogle ScholarPubMed
Kertesz, A., Nadkarni, N., Davidson, W. and Thomas, A. W. (2000). The Frontal Behavioural Inventory in the differential diagnosis of frontotemporal dementia. Journal of the International Neuropsychological Society, 6, 460468.CrossRefGoogle ScholarPubMed
Kertesz, A., McMonagle, P., Blair, M., Davidson, W. and Munoz, D. G. (2005). The evolution and pathology of frontotemporal dementia. Brain, 128, 19962005.CrossRefGoogle ScholarPubMed
Knibb, J. A., Xuereb, J. H., Patterson, K. and Hodges, J. R. (2006). Clinical and pathological characterization of progressive aphasia. Annals of Neurology, 59, 156165.CrossRefGoogle ScholarPubMed
Knopmann, D. S. et al. (2005). Antemortem diagnosis of frontotemporal lobar degeneration. Annals of Neurology, 57, 480488.CrossRefGoogle Scholar
Lebert, F., Pasquier, F., Souliez, L. and Petit, H. (1998). Frontotemporal behavioural scale. Alzheimer's Disease and Associated Disorders, 12, 335339.CrossRefGoogle Scholar
Liscic, R. M., Storandt, M., Cairns, N. J. and Morris, J. C. (2007). Clinical and psychometric distinction of frontotemporal and Alzheimer dementias. Archives of Neurology, 64, 535540.CrossRefGoogle ScholarPubMed
Lopez, O. L. et al. (2000). Research evaluation and diagnosis of probable Alzheimer's disease over the last two decades: I. Neurology, 55, 18541862.CrossRefGoogle ScholarPubMed
Lund and Manchester Groups (1994). The Lund Manchester Consensus Statement: clinical and neuropathological criteria for frontotemporal dementia. Journal of Neurology, Neurosurgery and Psychiatry, 57, 416418.CrossRefGoogle Scholar
Marczinski, C. A., Davidson, W. and Kertesz, A. (2004). A longitudinal study of behaviour in frontotemporal dementia and primary progressive aphasia. Cognitive and Behavioral Neurology, 17, 185190.Google ScholarPubMed
Mega, M. S. et al. (1996). The spectrum of behavioural changes in Alzheimer's disease. Neurology, 46, 130135.CrossRefGoogle ScholarPubMed
Mendez, M. F., Perryman, K. M., Miller, B. L. and Cummings, J. L. (1998). Behavioural differences between frontotemporal dementia and Alzheimer's disease: a comparison on the BEHAVE-AD rating scale. International Psychogeriatrics, 10, 155162.CrossRefGoogle ScholarPubMed
Morris, J. C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43: 24122414.CrossRefGoogle ScholarPubMed
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G. and Kokmen, E. (1999). Mild cognitive impairment: clinical characterization and outcome. Archives of Neurology, 56, 303308.CrossRefGoogle ScholarPubMed
Price, B. H., Gurvit, H., Weintraub, S., Geula, C., Leimkuhler, E. and Mesulam, M. (1993). Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease. Archives of Neurology, 50, 931937.CrossRefGoogle ScholarPubMed
Rosen, W. G., Mohs, R. C. and Davis, K. L. (1984). A new rating scale for Alzheimer's disease. American Journal of Psychiatry, 141, 356364.Google ScholarPubMed
Royall, D. R., Mahurin, R. K. and Cornell, J. (1994). Bedside assessment of frontal degeneration: distinguishing Alzheimer's disease from non-Alzheimer's cortical dementia. Experimental Aging Research, 20, 95103.CrossRefGoogle ScholarPubMed
Slachevsky, A., Villalpando, J. M., Sarazin, M., Hahn-Barma, V., Pillon, B. and Dubois, B. (2004). Frontal Assessment Battery and differential diagnosis of fronto-temporal dementia and Alzheimer's disease. Archives of Neurology, 61, 11041107.CrossRefGoogle Scholar
Stern, Y., Mayeux, R., Sano, M., Hauser, W. A. and Bush, T. (1987). Predictors of disease course in patients with probable Alzheimer's disease. Neurology, 37, 16491653.CrossRefGoogle ScholarPubMed
Storey, E., Slavin, M. and Kinsella, G. J. (2002). Patterns of cognitive impairment in Alzheimer's disease: assessment and differential diagnosis. Frontiers in Bioscience, 7, 155184.Google ScholarPubMed
Sunderland, T. et al. (1989). Clock drawing in Alzheimer's disease: a novel measure of dementia severity. Journal of the American Geriatrics Society, 37, 725729.CrossRefGoogle ScholarPubMed
van der Zee, J., Sleegers, K. and Van Broeckhoven, C. (2008). The Alzheimer disease frontotemporal lobar degeneration spectrum. Neurology, 71, 11911197.CrossRefGoogle ScholarPubMed
Varma, A. R., Snowden, J. S., Lloyd, J. J., Talbot, P. R., Mann, D. M. A. and Neary, D. (1999). Evaluation of the NINCDS-ADRDA criteria in the differentiation of Alzheimer's disease and frontotemporal dementia. Journal of Neurology, Neurosurgery and Psychiatry, 66, 184188.CrossRefGoogle ScholarPubMed
Welsh, K., Butters, N., Hughes, J., Mohs, R. and Heyman, A. (1991). Detection of abnormal memory decline in mild cases of Alzheimer's disease using CERAD neuropsychological measures. Archives of Neurology, 48, 278281.CrossRefGoogle ScholarPubMed
Woodward, M. C. and Woodward, E. (2009). A national survey of memory clinics. International Psychogeriatrics, 21, 696702CrossRefGoogle ScholarPubMed
Woodward, M. C., Hsiung, R. G.-K., Feldman, H., Jacova, C. and Mackenzie, I. R. (2010a). High prevalence of multiple brain pathologies in dementia. European Geriatric Medicine (in press).CrossRefGoogle Scholar
Woodward, M. C., Jacova, C., Black, S., Kertesz, A., Mackenzie, I. R. and Feldman, H. H. (2010b). Differentiating the frontal variant of Alzheimer's disease. International Journal of Geriatric Psychiatry, 25, 732738.CrossRefGoogle ScholarPubMed