TY - JOUR
T1 - Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to apoe genotype
AU - Albert, Marilyn
AU - Soldan, Anja
AU - Gottesman, Rebecca
AU - McKhann, Guy
AU - Sacktor, Ned
AU - Farrington, Leonie
AU - Grega, Maura
AU - Turner, Raymond
AU - Lu, Yi
AU - Li, Shanshan
AU - Wang, Mei Cheng
AU - Selnes, Ola
N1 - Publisher Copyright:
© 2014 Bentham Science Publishers.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Background: This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes. Methods: Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/- 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined. Results: Lower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/- 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers. Conclusions: Cognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.
AB - Background: This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes. Methods: Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/- 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined. Results: Lower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/- 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers. Conclusions: Cognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.
KW - Apolipoprotein E genotype
KW - Cognitive decline
KW - Episodic memory
KW - Longitudinal follow-up
KW - Mild cognitive impairment
KW - Preclinical alzheimer’s disease
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U2 - 10.2174/156720501108140910121920
DO - 10.2174/156720501108140910121920
M3 - Article
C2 - 25212916
AN - SCOPUS:84926167473
VL - 11
SP - 773
EP - 784
JO - Current Alzheimer Research
JF - Current Alzheimer Research
SN - 1567-2050
IS - 8
ER -