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Differential cognitive deterioration in dementia: a two year longitudinal study

Differential cognitive deterioration in dementia: a two year longitudinal study
Differential cognitive deterioration in dementia: a two year longitudinal study

The ability to predict cognitive deterioration in patients with dementia holds valuable potential for clinical trials and early intervention. This study identified cognitive domains deteriorating differentially over time as well as baseline predictors of subsequent cognitive decline in patients referred to a memory clinic. Twenty-six subjects with Alzheimer's disease (AD) and 43 subjects with Subjective Memory Impairment (SMI) were entered into a longitudinal study in which cognitive function was assessed at baseline and at 8-monthly intervals for 2 years, using a range of well-validated measures. Thirty-seven patients with depression and 39 healthy controls were also longitudinally assessed. AD was associated with disproportionate deterioration over time on general measures of cognitive function, multiple measures of mnemonic processing, mental fluency (letter and category), and aspects of motor speed. SMI showed restricted relative cognitive deterioration on general measures of cognitive function, on a subset of memory measures, and on letter but not category fluency. Secondary analysis showed that earliest detectable ADAS-cog and MMSE decline in AD was at 16 months, while several specific neuropsychological indices were sensitive as early as 8 months (graded naming test, semantic naming, and the category/letter fluency tests). In combination, baseline/early changes in cognitive performance, alongside clinical measures, predicted 48% of disease progression over two years in memory impaired patients as a whole. These findings have implications for identifying patients likely to benefit from disease modifying agents, and for designing, powering, enriching, and implementing future clinical trials. Follow-up studies in independent populations are needed to validate predictive algorithms identified.

Alzheimer's disease, cognition, dementia, enrichment, longitudinal, prediction, semantic
1387-2877
125-136
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Blackwell, Andrew D.
1866c337-e426-424a-bbf9-aeb2d962f0aa
Nathan, Pradeep J.
8862816e-472e-49b4-9c74-c89faffd7f10
Hammond, Geoff
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Robbins, Trevor W.
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Hodges, John R.
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Michael, Albert
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Semple, James M.
496d7a53-1ad3-46e3-a698-6a8fd376d2e7
Bullmore, Edward T.
f2fa4f13-15e7-4d71-a4ca-f66d291a31a8
Sahakian, Barbara J.
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Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Blackwell, Andrew D.
1866c337-e426-424a-bbf9-aeb2d962f0aa
Nathan, Pradeep J.
8862816e-472e-49b4-9c74-c89faffd7f10
Hammond, Geoff
636af4e2-53fb-4e47-9bd7-cf5e43a3474e
Robbins, Trevor W.
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Hodges, John R.
7e7a95ab-a65f-42a1-8c01-30917e6b2f3d
Michael, Albert
c7e6fb1c-561a-4352-a0e3-e6d2b5f4e943
Semple, James M.
496d7a53-1ad3-46e3-a698-6a8fd376d2e7
Bullmore, Edward T.
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Sahakian, Barbara J.
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Chamberlain, Samuel R., Blackwell, Andrew D., Nathan, Pradeep J., Hammond, Geoff, Robbins, Trevor W., Hodges, John R., Michael, Albert, Semple, James M., Bullmore, Edward T. and Sahakian, Barbara J. (2011) Differential cognitive deterioration in dementia: a two year longitudinal study. Journal of Alzheimer's Disease, 24 (1), 125-136. (doi:10.3233/JAD-2010-100450).

Record type: Article

Abstract

The ability to predict cognitive deterioration in patients with dementia holds valuable potential for clinical trials and early intervention. This study identified cognitive domains deteriorating differentially over time as well as baseline predictors of subsequent cognitive decline in patients referred to a memory clinic. Twenty-six subjects with Alzheimer's disease (AD) and 43 subjects with Subjective Memory Impairment (SMI) were entered into a longitudinal study in which cognitive function was assessed at baseline and at 8-monthly intervals for 2 years, using a range of well-validated measures. Thirty-seven patients with depression and 39 healthy controls were also longitudinally assessed. AD was associated with disproportionate deterioration over time on general measures of cognitive function, multiple measures of mnemonic processing, mental fluency (letter and category), and aspects of motor speed. SMI showed restricted relative cognitive deterioration on general measures of cognitive function, on a subset of memory measures, and on letter but not category fluency. Secondary analysis showed that earliest detectable ADAS-cog and MMSE decline in AD was at 16 months, while several specific neuropsychological indices were sensitive as early as 8 months (graded naming test, semantic naming, and the category/letter fluency tests). In combination, baseline/early changes in cognitive performance, alongside clinical measures, predicted 48% of disease progression over two years in memory impaired patients as a whole. These findings have implications for identifying patients likely to benefit from disease modifying agents, and for designing, powering, enriching, and implementing future clinical trials. Follow-up studies in independent populations are needed to validate predictive algorithms identified.

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More information

Accepted/In Press date: 15 November 2010
Published date: 29 March 2011
Keywords: Alzheimer's disease, cognition, dementia, enrichment, longitudinal, prediction, semantic

Identifiers

Local EPrints ID: 492892
URI: http://eprints.soton.ac.uk/id/eprint/492892
ISSN: 1387-2877
PURE UUID: 51a8dd10-b515-40c1-9005-3cf2ad21e44f
ORCID for Samuel R. Chamberlain: ORCID iD orcid.org/0000-0001-7014-8121

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Date deposited: 19 Aug 2024 16:49
Last modified: 20 Aug 2024 01:59

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Contributors

Author: Samuel R. Chamberlain ORCID iD
Author: Andrew D. Blackwell
Author: Pradeep J. Nathan
Author: Geoff Hammond
Author: Trevor W. Robbins
Author: John R. Hodges
Author: Albert Michael
Author: James M. Semple
Author: Edward T. Bullmore
Author: Barbara J. Sahakian

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