Association of parental dementia with cognitive and brain MRI measures in middle-aged adults

S. Debette, P. A. Wolf, A. Beiser, R. Au, J. J. Himali, A. Pikula, S. Auerbach, Charles DeCarli, S. Seshadri

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Abstract

OBJECTIVES:: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort. METHODS:: A total of 717 Framingham offspring (mean age: 59 ± 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally. RESULTS:: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE ε4 status (p < 0.002). In APOE ε4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta =-1.81 ± 0.53, p < 0.001) and visuospatial memory (beta =-1.73 ± 0.47, p < 0.001). These associations were stronger for parental AD (beta =-1.97 ± 0.52, p < 0.001, beta =-1.95 ± 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE ε4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE ε4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04). CONCLUSIONS:: Among middle-aged carriers of the APOE ε4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.

Original languageEnglish (US)
Pages (from-to)2071-2078
Number of pages8
JournalNeurology
Volume73
Issue number24
DOIs
StatePublished - Dec 2009

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Dementia
Brain
Alzheimer Disease
Odds Ratio
Executive Function
Atrophy
Multivariate Analysis
Alleles
Mutation

ASJC Scopus subject areas

  • Clinical Neurology

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Debette, S., Wolf, P. A., Beiser, A., Au, R., Himali, J. J., Pikula, A., ... Seshadri, S. (2009). Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. Neurology, 73(24), 2071-2078. https://doi.org/10.1212/WNL.0b013e3181c67833

Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. / Debette, S.; Wolf, P. A.; Beiser, A.; Au, R.; Himali, J. J.; Pikula, A.; Auerbach, S.; DeCarli, Charles; Seshadri, S.

In: Neurology, Vol. 73, No. 24, 12.2009, p. 2071-2078.

Research output: Contribution to journalArticle

Debette, S, Wolf, PA, Beiser, A, Au, R, Himali, JJ, Pikula, A, Auerbach, S, DeCarli, C & Seshadri, S 2009, 'Association of parental dementia with cognitive and brain MRI measures in middle-aged adults', Neurology, vol. 73, no. 24, pp. 2071-2078. https://doi.org/10.1212/WNL.0b013e3181c67833
Debette, S. ; Wolf, P. A. ; Beiser, A. ; Au, R. ; Himali, J. J. ; Pikula, A. ; Auerbach, S. ; DeCarli, Charles ; Seshadri, S. / Association of parental dementia with cognitive and brain MRI measures in middle-aged adults. In: Neurology. 2009 ; Vol. 73, No. 24. pp. 2071-2078.
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abstract = "OBJECTIVES:: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort. METHODS:: A total of 717 Framingham offspring (mean age: 59 ± 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally. RESULTS:: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE ε4 status (p < 0.002). In APOE ε4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta =-1.81 ± 0.53, p < 0.001) and visuospatial memory (beta =-1.73 ± 0.47, p < 0.001). These associations were stronger for parental AD (beta =-1.97 ± 0.52, p < 0.001, beta =-1.95 ± 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE ε4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE ε4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04). CONCLUSIONS:: Among middle-aged carriers of the APOE ε4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.",
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T1 - Association of parental dementia with cognitive and brain MRI measures in middle-aged adults

AU - Debette, S.

AU - Wolf, P. A.

AU - Beiser, A.

AU - Au, R.

AU - Himali, J. J.

AU - Pikula, A.

AU - Auerbach, S.

AU - DeCarli, Charles

AU - Seshadri, S.

PY - 2009/12

Y1 - 2009/12

N2 - OBJECTIVES:: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort. METHODS:: A total of 717 Framingham offspring (mean age: 59 ± 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally. RESULTS:: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE ε4 status (p < 0.002). In APOE ε4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta =-1.81 ± 0.53, p < 0.001) and visuospatial memory (beta =-1.73 ± 0.47, p < 0.001). These associations were stronger for parental AD (beta =-1.97 ± 0.52, p < 0.001, beta =-1.95 ± 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE ε4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE ε4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04). CONCLUSIONS:: Among middle-aged carriers of the APOE ε4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.

AB - OBJECTIVES:: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort. METHODS:: A total of 717 Framingham offspring (mean age: 59 ± 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally. RESULTS:: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE ε4 status (p < 0.002). In APOE ε4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta =-1.81 ± 0.53, p < 0.001) and visuospatial memory (beta =-1.73 ± 0.47, p < 0.001). These associations were stronger for parental AD (beta =-1.97 ± 0.52, p < 0.001, beta =-1.95 ± 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE ε4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE ε4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04). CONCLUSIONS:: Among middle-aged carriers of the APOE ε4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.

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