Slower speed-of-processing of cognitive tasks is associated with
presence of the apolipoprotein e4 allele
, Barbara Sommer
, Nate Way
, Helena C. Kraemer
, Greer Murphy
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA 94305-5550, United States
VA Palo Alto Health Care System, Palo Alto, CA, United States
Received 10 March 2004; received in revised form 29 November 2006; accepted 4 December 2006
Detection of preclinical cognitive deﬁcits is important for identifying those at greatest risk for such disorders as Alzheimer’s disease.
However, available neuropsychological measures may not be suﬃciently sensitive to preclinical cognitive impairment, particularly in high
functioning or younger older adults. This study utilizes a battery of computerized cognitive tests (Cognometer) designed to provide a
more sensitive measure of age-related cognitive performance by incorporating speed-of-processing components. Fifty-one community-
dwelling older adults were administered the Cognometer battery, which incorporates speed-of-processing components into measures
of verbal, spatial and working memory, attention, and visuo-spatial ability. Performance of 18 subjects with the e4 allele was compared
to that of 33 subjects without the e4 allele. A brief battery of standard neuropsychological measures was also administered. No signiﬁcant
diﬀerences were observed between the two groups with respect to performance on any of the neuropsychological measures. However,
with respect to the Cognometer battery, individuals with the e4 allele were signiﬁcantly slower in performing all the cognitive tasks, with
the exception of the visuo-spatial task. With respect to performance, the two genotype groups did not diﬀer signiﬁcantly except on imme-
diate memory, with the e4 group exhibiting increased errors. Overall, the e4 group was signiﬁcantly slower in performing all of the Cog-
nometer memory tasks. These ﬁndings provide continued support for the negative impact of the e4 allele on cognition and further suggest
that speed-of-processing during memory tasks may have the potential to detect subtle cognitive deﬁcits.
Ó 2006 Published by Elsevier Ltd.
Keywords: Apolipoprotein e4 allele; Speed-of-processing; Memory and aging
Age-related changes in memory and cognition are well
documented. Such deﬁcits are also the hallmark of many
age-related illnesses such as vascular dementia and Alzhei-
mer’s disease (AD). AD accounts for 50–70% of cases in
older patients and is the cause of more than 100,000 deaths
yearly (Albert and Moss, 1988; Evans et al., 1997; Lendon
et al., 1997). Mid-range costs for each AD patient are cur-
rently estimated at more than $47,500 over the course of
the illness, with total cost to the nation estimated at
$82.7 billion per year (O’Hara et al., 2001).
Detection of preclinical cognitive changes related to AD
is important for the identiﬁcation of those who are at great-
est risk and are most likely to beneﬁt from palliative and
preventative therapies. However, early detection of AD
has proved problematic and several investigators have sug-
gested that available neuropsychological measures may not
be sensitive to decline, particularly in high functioning and/
0022-3956/$ - see front matter Ó 2006 Published by Elsevier Ltd.
This work was supported in part by Cognitive Care Inc., the Brookdale
Foundation Group; the Center for Gender-Based Health Research,
Institute for Research on Women and Gender, Stanford University; the
VA Sierra-Paciﬁc Mental Illness Research, Education and Clinical Center
(MIRECC), the Medical Research Service of the VA Palo Alto Health
Care System, and by National Institutes of Health grants AG 18784;
MH35182; MH40041; AG17824.
Corresponding author. Tel.: +1 650 852 3287; fax: +1 650 852 3297.
E-mail address: firstname.lastname@example.org (R. O’Hara).
Available online at www.sciencedirect.com
Journal of Psychiatric Research 42 (2008) 199–204