Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: A replication study

Richard J. Caselli, David Osborne, Eric M. Reiman, Joseph G. Hentz, Carolyn J. Barbieri, Ann M. Saunders, John Hardy, Neill R. Graff-Radford, Geri R. Hall, Gene E. Alexander

Research output: Contribution to journalArticle

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Abstract

In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9±5.9 years), gender (60% women), and education (15.9±2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.

Original languageEnglish (US)
Pages (from-to)93-98
Number of pages6
JournalJournal of the Neurological Sciences
Volume189
Issue number1-2
DOIs
StatePublished - Aug 15 2001

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Apolipoprotein E4
Homozygote
Heterozygote
Intelligence
Repression (Psychology)
Education
Newspapers
Neuropsychological Tests
Neurologic Examination
Frontal Lobe
Short-Term Memory
Psychiatry
Cognitive Dysfunction
Cross-Sectional Studies
Depression

Keywords

  • Aging
  • Alzheimer's disease
  • Apolipoprotein E
  • Frontal lobe
  • Memory
  • Preclinical

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes : A replication study. / Caselli, Richard J.; Osborne, David; Reiman, Eric M.; Hentz, Joseph G.; Barbieri, Carolyn J.; Saunders, Ann M.; Hardy, John; Graff-Radford, Neill R.; Hall, Geri R.; Alexander, Gene E.

In: Journal of the Neurological Sciences, Vol. 189, No. 1-2, 15.08.2001, p. 93-98.

Research output: Contribution to journalArticle

Caselli, RJ, Osborne, D, Reiman, EM, Hentz, JG, Barbieri, CJ, Saunders, AM, Hardy, J, Graff-Radford, NR, Hall, GR & Alexander, GE 2001, 'Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: A replication study', Journal of the Neurological Sciences, vol. 189, no. 1-2, pp. 93-98. https://doi.org/10.1016/S0022-510X(01)00577-9
Caselli, Richard J. ; Osborne, David ; Reiman, Eric M. ; Hentz, Joseph G. ; Barbieri, Carolyn J. ; Saunders, Ann M. ; Hardy, John ; Graff-Radford, Neill R. ; Hall, Geri R. ; Alexander, Gene E. / Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes : A replication study. In: Journal of the Neurological Sciences. 2001 ; Vol. 189, No. 1-2. pp. 93-98.
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