Decline in verbal memory during preclinical Alzheimer's disease: Examination of the effect of APOE genotype

Abstract

A subtle decline in episodic memory often occurs prior to the emergence of the full dementia syndrome in nondemented older adults who develop Alzheimer's disease (AD). The APOE-epsilon4 genotype may engender a more virulent form of AD that hastens this decline. To examine this possibility, we compared the rate of decline in episodic memory during the preclinical phase of AD in individuals with or without at least one APOE epsilon4 allele. Nondemented normal control (NC; n = 84) participants, nondemented older adults who subsequently developed dementia within 1 or 2 years (i.e., preclinical AD; n = 20), and patients with mild AD (n = 53) were examined with 2 commonly employed tests of episodic memory, the Logical Memory subtest of the Wechsler Memory Scale-Revised and the California Verbal Learning Test. Results revealed a precipitous decline in verbal memory abilities 1 to 2 years prior to the onset of the dementia syndrome, but there was little effect of APOE genotype on the rate of this memory decline. The presence of an APOE-epsilon4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD.

Apolipoprotein E epsilon 4 (APOE‐ε4) genotype is associated with decreased 6‐month verbal memory performance after mild traumatic brain injury

“…Similar results have been described in AD patients with left temporal and/or hippocampal damage, where a subtle decline in episodic memory occurs prior to the emergence of full dementia. The presence of the APOE‐ ε 4 allele increases deposition of beta‐amyloid plaques, and has been shown to independently contribute to the prediction of conversion dementia when measured by tests of episodic memory such as the CVLT‐II (Lange et al., 2002). …”

Neuropsychological deficits associated with Alzheimer's disease in the very-old: Discrepancies in raw vs. standardized scores

“…Numerous studies have now shown that subtle cognitive changes can precede the diagnosis of AD by a few years or more (Bäckman et al, 2001;Bondi et al, 1994Bondi et al, , 1995Bondi et al, , 1999Chen et al, 2001;Lange et al, 2002;Linn et al, 1995;Masur et al, 1994;Rubin et al, 1998;Small et al, 1998Small et al, , 2000Smith et al, 1998). As Sliwinski and colleagues (1996) have shown, the inclusion of such individuals with preclinical AD in a normative sample leads to an underestimate of the mean, an overestimate of the variance, and an overestimate of the effect of age on a given cognitive measure, all of which reduces the sensitivity of the measure for detecting mild impairment.…”

“…If this is the case, previously observed differences in the clinical and neuropsychological presentation of YoungOld AD patients with or without the ε4 allele (Lange et al, 2002;Smith et al, 1998) may be absent or changed in Very-Old AD patients. Several studies that have compared cognitive deficits in predominantly Young-Old AD patients with or without the ε4 allele suggest that those with the ε4 allele may have generally more severe memory impairment (Smith et al, 1998) or less ability to use strategic processes or semantic abilities in support of memory (Lange et al, 2002) than those without the ε4 allele, even when duration of illness and severity of global dementia is comparable. A decrease in the influence of the APOE ε4 allele on the manifestation of AD in the Very-Old may attenuate these differences and modify the profile of cognitive deficits that characterizes the disease.…”

Progressive impairment on neuropsychological tasks in a longitudinal study of preclinical Alzheimer's disease.

“…Some of the free recall data for the CONVs presented in Table 2 were previously analyzed by Lange et al (2002) as part of an unrelated investigation of the effect of apolipoprotein E (ApoE) genotype on verbal memory. Unless otherwise noted, an alpha level of .05 was used throughout.…”