The Course and End-Points of Alzheimer’s Disease According to Sociodemographics, Apolipoprotein e Genotype and Cognitive Ability (original) (raw)
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Dementia and Geriatric Cognitive Disorders, 2004
The presence of the apolipoprotein E (APOE) Â4 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 Â4 allele on the different ages at the onset of the disease, we split the study sample into two groups:
Dementia and Geriatric Cognitive Disorders, 2004
The presence of the apolipoprotein E (APOE) Â4 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 Â4 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 Â4 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 Â4 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 Â4 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: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease
Journal of Neurology Neurosurgery and Psychiatry, 1996
OBJECTIVES: To determine the association between the epsilon2 and epsilon4 alleles of apolipoprotein E (ApoE) and independent measures of cognitive decline and non-cognitive symptomatology in late onset Alzheimer's disease. METHODS: The frequency of the epsilon2 and epsilon4 alleles of ApoE and their association with measures of cognitive decline and non-cognitive symptomatology were assessed in a population based case register study
The influence of Apolipoprotein E genotype on regional pathology in Alzheimer’s disease
BMC Neurology, 2013
Background: Carriers of the ApoE ε4 allele are at a greater risk for developing Alzheimer's disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among ε4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency. Methods: 566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE ε4 carriers and 254 ApoE ε4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (ε4 carrier vs. ε4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal). Results: ε4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than ε4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE ε4 carrier status, ε4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, ε4 carriers tended to have significantly more "frequent" scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older. Conclusions: ApoE ε4 carriers had a significantly higher percentage of "frequent" scores for plaques and tangles when compared to ApoE ε4 non-carriers for several brain regions. However, ε4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.
Neuroscience Letters, 2000
The concentration of beta-Amyloid (1±42) protein (Ab42) in cerebrospinal¯uid (CSF) was determined in 75 Alzheimer's disease (AD) patients, 35 patients with other causes of dementia and 30 cognitively healthy age-matched controls. A signi®cant decrease of Ab42 concentration was found in AD patients, even in 25 subjects with very mild dementia as compared to patients with other causes of dementia and controls. Within AD patients we observed a signi®cant decline of Ab42 from very mild to mild and moderate dementia. In addition, Ab42 levels were negatively correlated with the severity of cognitive impairment and with the number of 14 alleles inherited. We conclude that measurement of Ab42 in CSF might be helpful for identifying AD at an early stage and also for tracking the clinical course.
Apolipoprotein eϵ4, other risk factors, and course of alzheimer’s disease
Biological Psychiatry, 1999
Background: The ⑀4 allele of apolipoprotein E (apoE ⑀4) is associated with late-onset Alzheimer's disease (AD), but its relationship to various aspects of AD has become increasingly unclear. We studied the relationship of apoE genotype in AD to educational attainment, history of heart disease or head injury, age of onset, gender, severity of illness, depression, psychotic symptoms, rate of dementia progression, and time from initial evaluation to nursing home placement. Methods: ApoE ⑀4 genotype was determined for 97 clinically diagnosed AD patients and 61 neuropathologically confirmed cases of AD. Results: Presence of one or more ⑀4 alleles occurred in 66% of AD cases as compared with 27% in control subjects (allele frequency was .40 for AD, .15 for control subjects). Among AD subjects there was no significant relationship between ⑀4 alleles and educational attainment, history of heart disease, head injury, age of onset, severity of illness, depression, history of depression, rate of dementia progression, or time to nursing home placement. Marginal correlations emerged between number of ⑀4 alleles, and delusions (p ϭ .05) and hallucinations (p ϭ .05). There was a trend toward increased ⑀4 homozygosity in patients with onset between ages 65 and 70 years. Conclusions: We did not find that individuals with one or two apoE ⑀4 alleles differed significantly in clinical course of AD from those without ⑀4 except for a trend toward increased psychotic symptoms in the group as a whole and an increase in ⑀4 homozygosity in patients with reported symptom onset in the late 60s.
Annals of Neurology, 1995
A strong association has been described in cross-sectional studies between the ε4 allele of the apolipoprotein E and late-onset Alzheimer's disease (LOAD). This study addresses the relationship between disease progression and the ε4 allele in 62 sporadic LOAD (onset at age 70 and over) patients. Disease progression was estimated retrospectively with the Mini-Mental State Examination (MMSE) amounting to 4.7, 3.8, and 2.2 points per year (sex-adjusted test for trend: p = 0.01) and with the Clinical Dementia Rating (CDR) to 0.76, 0.67, and 0.42 units per year (p = 0.03) in -/-, ε4/-, and ε4/ε4 patients. The proportion of patients with fast progression decreased (p ≤ 0.005) and with slow progression increased (p = 0.002) with increasing ε4 gene dose. These findings were confirmed in a smaller sample of 28 patients for whom longitudinal assessments of MMSE were available and when nonlinear progression of the disease was accounted for in a stratified analysis. These data suggest that disease duration might be longer in ε4 carriers and that this might at least partly account for the cross-sectional association between the ε4 allele and LOAD.