Apolipoprotein E ε4 Allele Differently Affects the Patterns of Neuropsychological Presentation in Early- and Late-Onset Alzheimer’s Disease Patients

Abstract

The presence of the apolipoprotein E (APOE) Ε4 allele is a definite risk factor for the onset of Alzheimer’s disease (AD). Its presence seems to affect especially the memory in the early stage of the disease, but the effect on the progression of the disease and survival is still controversial. Some longitudinal studies could be influenced by variables other than APOE, such as the response to medical treatment, rehabilitation therapy and inclusion of patients at different stages of progression at baseline. Moreover, the inclusion in the same study sample of patients of different ages at onset of the disease (below 65 or above 80 years) appears arbitrary. In our study, we evaluated a population of newly diagnosed untreated AD patients at their first neuropsychological examination and with the onset of their first symptoms not longer than 3 years ago. In order to analyse the different effects of the APOE Ε4 allele on the different ages at the onset of the disease, we split the study sample into two groups: (1) subjects under 65 years [early-onset AD (EOAD); n = 30] and subjects over 70 years [late-onset AD (LOAD); n = 41], excluding subjects with an age of onset between 66 and 69 years. Our results show that the APOE Ε4 allele carriers are characterised by a different neuropsychological pattern at the disease onset; however, only in the EOAD group is this effect significant: in EOAD, the Ε4 allele carriers obtained worse performances in learning, long-term verbal memory and general intelligence tasks. On the contrary, in LOAD patients, the pattern of cognitive impairment at the onset is not dependent on the possession of an Ε4 allele in the genotype. Such data could suggest a careful control of the study sample concerning age at the onset of the disease since APOE could play a different role in EOAD and LOAD mainly due to the different pathogenic mechanism at the onset and evolution of AD.

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

“…In AD patients, this finding agrees with the available literature, showing an inconsistent effect of apoE genotype on clinical severity at presentation (30,31). The majority of longitudinal studies, although, have shown that 4 is associated with more rapid cognitive decline in AD (4).…”

Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease

“…The present findings echo threads of some of the extant literature. Several studies have reported that ε4 carriers display poorer episodic memory (24)(25)(26)(27) and smaller hippocampal or other MTL volumes (17-21, 33) than noncarriers. Within the present CSF-restricted sample in which carriers and noncarriers were well matched for age and mild disease severity, we observed similar findings.…”

“…Perhaps the most consistent finding is the presence of greater impairment of delayed recall on episodic memory tasks in ε4 carriers relative to noncarriers (24)(25)(26)(27), although, again, conflicting results have been reported (17,18). Findings are inconsistent regarding whether there are domains of greater cognitive impairment in noncarriers relative to carriers, with some indication that noncarriers may display greater difficulty on tasks of attention, executive, or verbal functions (17,25,26).…”

APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease

“…Given its role in disease onset (3), the apolipoprotein E (APOE) ε4 allele may contribute to differential rates of cognitive decline in AD; however, this hypothesis has been explored for over ten years with no resolution. ε4 carriers have been found to demonstrate both slower (4)(5)(6) and faster rates of decline (7)(8)(9)(10)(11)(12)(13), potentially reflecting methodological differences in recruitment techniques, the measurement of cognition, followup time, and participants' stage of dementia. A subset of studies has also demonstrated nondifferential rates of decline in relation to ε4 status (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24); however, most of these studies had relatively small sample sizes which may have limited their ability to detect differential change over time.…”