APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease
NeurologyPublished 10 April 2008Open access
Stephanie Cosentino, Nikolaos Scarmeas, Elizabeth Helzner, M. Maria Glymour, Jason Brandt, M. Albert
Citations217
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TL;DR
APOE ε4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease, particularly in the incident population-based AD group.
Abstract
OBJECTIVE: To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). METHODS: Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. RESULTS: The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. CONCLUSION: APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.
Keywords
MedicineNeuroscience
Journal of Psychiatric Research“Mini-mental state”
86,858 Citations1975Marshal F. Folstein, Susan E. Folstein +1 more
A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
NeurologyClinical diagnosis of Alzheimer's disease
27,993 Citations1984Guy M. McKhann, David A. Drachman +4 more
The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
PubMed[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].
20,872 Citations1997Nobutsugu Hirono, Etsuro Mori +6 more
Dementia and Geriatric Cognitive Disorders ExtraSpecial Care Units and Traditional Care in Dementia: Relationship with Behavior, Cognition, Functional Status and Quality of Life - A Review
20,660 Citations2013Jeroen S. Kok, Ina J. Berg +1 more
Overall, patients with dementia who lived at special care units (SCUs) showed a significantly more challenging behavior, more agitation/aggression, more depression and anxiety, more cases of global cognitive impairment and a better psychosocial functioning.
GerontologyOlder Adults' Reasons for Using Technology while Aging in Place
19,749 Citations2015Sebastiaan Theodorus Michaël Peek, Katrien Luijkx +7 more
GerontologySensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
18,959 Citations2014Maarit Kangas, Raija Korpelainen +3 more
Evaluating the long-term fall detection sensitivity and false alarm rate of a fall detection prototype in real-life use suggests that automatic accelerometric fall detection systems might offer a tool for improving safety among older people.
BiometrikaLongitudinal data analysis using generalized linear models
18,123 Citations1986Kung‐Yee Liang, Scott L. Zeger
ScienceGene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
9,464 Citations1993Elizabeth H. Corder, Ann M. Saunders +7 more
APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
Proceedings of the National Academy of SciencesApolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
4,286 Citations1993Warren J. Strittmatter, Ann M. Saunders +5 more
It is demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease.
NeurologyAssociation of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
3,780 Citations1993Ann M. Saunders, Warren J. Strittmatter +12 more
Data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD and suggest it may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
JAMAInfluence of Education and Occupation on the Incidence of Alzheimer's Disease
1,423 Citations1994Yaakov Stern
Increased educational and occupational attainment may reduce the risk of incident AD, either by decreasing ease of clinical detection of AD or by imparting a reserve that delays the onset of clinical manifestations.
NeurologyCognitive activity and incident AD in a population-based sample of older persons
452 Citations2002R. J. Wilson, David A. Bennett +6 more
Frequency of participation in cognitively stimulating activities appears to be associated with risk of AD and may partially explain the association of educational and occupational attainment with disease risk.
NeurologyThe Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
438 Citations1993John C. Morris, S. D. Edland +7 more
It is found that rate-of-change determinations are less reliable when the observation period is 1 year or less, dementia progression may be nonlinear when described by certain measures, and that simple change scores do not accurately characterize the rate of decline.
Annals of NeurologyClinical and pathological correlates of apolipoprotein E ε4 in Alzheimer's disease
380 Citations1996Teresa Gómez‐Isla, Howard West +7 more
Analysis of clinical parameters compared with apoE genotype showed that the ε4 allele is associated with an earlier age of onset but no change in rate of progression of dementia, and hypotheses that focus on an influence of apolipoprotein Eε4 on amyloid deposition are supported.
Archives of NeurologyDiagnosis of Dementia in a Heterogeneous Population
370 Citations1992Yaakov Stern
The findings suggest that the neuropsychological battery may have utility in the diagnosis of dementia, however, neuro psychological performance may be influenced by education, and some form of adjustment, such as correction for activities of daily living, may be required in epidemiological studies.
Journal of Neurology Neurosurgery & PsychiatryEducation and rates of cognitive decline in incident Alzheimer's disease
341 Citations2005Nikolaos Scarmeas
It is concluded that higher education AD patients experience faster cognitive decline, which was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity.
NeurologyEarly diagnosis of herpes simplex encephalitis by MRI
339 Citations1987Gerhard Schroth, Joachim Gawehn +3 more
MRI is the most sensitive noninvasive test in early diagnosis of HSE due to its high sensitivity to inflammatory increased brain water content, and it is superior to CT in localizing the pathognomonic lesions of the limbic system.
Nature GeneticsAPOE genotype predicts when — not whether — one is predisposed to develop Alzheimer disease
335 Citations1998M.R. Meyer, JoAnn T. Tschanz +5 more
It is shown that the APOE genotype predicts when — not whether — one is predisposed to develop Alzheimer disease, but not how likely it is to happen.
Arteriosclerosis and Thrombosis A Journal of Vascular BiologyApolipoprotein E polymorphisms affect atherosclerosis in young males. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.
289 Citations1991James E. Hixson
Investigators in eight communities collected aortas, right coronary arteries, blood and liver samples, and associated information from 720 young males, aged 15-34 years, who died of external causes, suggesting that genotypic effects on arterial lesions may not be mediated entirely by changes in serum cholesterol concentrations.
Neurology<i>APOE</i> alleles predict the rate of cognitive decline in Alzheimer disease
208 Citations2005Carla Alexandra Ramalho de Sena Martins, Abderrahim Oulhaj +2 more
The decline shows a dose–response relation with the APOE ε4 allele, but the APoe ε2 allele is protective, and the nonlinear model yielded larger estimates of the maximal rate of decline than the linear.
NeurologyRates of progression in mild cognitive impairment and early Alzheimer’s disease
206 Citations2002Martha Storandt, Elizabeth Grant +2 more
The lack of effective predictors of the rate of dementia progression extends to the very earliest stages of the disease, including the stage currently identified as mild cognitive impairment (MCI), including what is often called MCI.
NeurologyA gender difference in the association between <i>APOE</i> genotype and age-related cognitive decline
171 Citations2001Erik Lykke Mortensen, Peter Høgh
The APOE ε4 allele is associated with normal age-related decline in cognitive functions in women only, and this finding may be supportive of recent evidence suggesting sex differences in APOE-associated risk for AD.
NeuroscienceApolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation
157 Citations1995Thomas G. Ohm, Mustafa Kırça +4 more
A histological staging system is set out which considers the gradual development of Alzheimer's disease-related histological changes over time and correlates highly with the cognitive decline ante mortem and revealed that both the mean stage for A4/beta-amyloid deposits and themean stage for neurofibrillary tangles get significantly shifted upwards in epsilon 4-carriers.
NeurologyAccelerated decline in apolipoprotein E-ϵ4 homozygotes with Alzheimer's disease
153 Citations1998Suzanne Craft, Linda Teri +6 more
Annals of NeurologyGene dose of the ε4 allele of apolipoprotein E and disease progression in sporadic late‐onset alzheimer's disease
151 Citations1995Giovanni B. Frisoni, Stefano Govoni +5 more
It is suggested that disease duration might be longer in ε4 carriers and that this might at least partly account for the cross‐sectional association between the ε 4 allele and LOAD.
NeurologyApolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease
151 Citations1996John H. Growdon, Joseph J. Locascio +3 more
The results indicate that the mechanism placing individuals with an epsilon 4 allele at risk for developing AD does not influence the rate of cognitive decline, and imply that the influence of apoE ePSilon 4 either precedes or occurs at an early point in the AD disease process.
Archives of NeurologyAssociation Between Apolipoprotein Eϵ4 and the Rate of Cognitive Decline in Community-Dwelling Elderly Individuals With and Without Dementia
140 Citations1998Cees Jonker, Ben Schmand +3 more
In a 4-year longitudinal study of subjects with a range of cognitive function, apoE e4 was associated with the rate of cognitive decline prior to the clinically symptomatic phase of dementia.
Journal of Neurology Neurosurgery & PsychiatryMajor decrease in the volume of the entorhinal cortex in patients with Alzheimer's disease carrying the apolipoprotein E epsilon 4 allele
132 Citations1998Kirsi Juottonen, Maarit Lehtovirta +3 more
Volumetric MRI measurements disclose that ApoE ε4 is associated with the degree of atrophy in the entorhinal cortex in early Alzheimer's disease, this effect being especially prominent in female patients with Alzheimer’s disease.
Annals of NeurologyThe absence of an apolipoprotein ϵ4 allele is associated with a more aggressive form of Alzheimer's disease
127 Citations1997Yaakov Stern, Jason Brandt +11 more
The results imply that APOE ϵ4 is associated with a less aggressive form of AD.
NeurologyRate of cognitive decline and mortality in Alzheimer’s disease
113 Citations2003Jeanette Hui, R. J. Wilson +4 more
Mortality in AD is strongly associated with rate of cognitive decline, and risk of death was increased more than threefold in the subgroup with mild decline, more than fivefold in those with moderately rapid decline,and more than eightfold inThose with the most rapid decline.
Archives of NeurologyAssociation of Apolipoprotein E Genotype and Alzheimer Disease in African Americans
110 Citations2006Jill R. Murrell, Brandon M. Price +9 more
The results suggest that other genetic factors and different environmental influences may play a role in the risk for AD in individuals of African ancestry.
Archives of NeurologyApolipoprotein E Genotype and Rate of Decline in Probable Alzheimer's Disease
108 Citations1996Elizabeth H. Corder, Lars Lannfelt +5 more
The ApoE genotype does not strongly influence the rate of decline in AD, implying that epsilon 4 might predispose to the development of the disease without accelerating its pathogenesis or progression.
Dementia and Geriatric Cognitive DisordersApolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis
91 Citations2006Timothy Kleiman, Kristina Zdanys +7 more
Although ApoE Ε4 increases the risk for AD and decreases the age of disease onset in population studies, it did not significantly influence the rate of disease progression in cognitive or functional domains in this AD patient sample.
Annals of NeurologyAccelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E ε4 allele
89 Citations2002Etsuro Mori, KangUk Lee +5 more
The involvement of the apolipoprotein E epsilon4 allele in the progression of hippocampal atrophy has implications for therapeutic approaches in Alzheimer's disease and should be taken into consideration in longitudinal studies including clinical drug trials.
American Journal of PsychiatryNo association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease
89 Citations1997Greer M. Murphy, John‐Paul Taylor +3 more
There is no support of a strong association between APOE epsilon 4 dosage and rate of cognitive decline in patients with Alzheimer's disease, and the ePSilon 4 allele did not predict age at onset.
Alzheimer Disease & Associated DisordersMulticenter Study of Predictors of Disease Course in Alzheimer Disease (the “Predictors Study”). I. Study Design, Cohort Description, and Intersite Comparisons
87 Citations1993Yaakov Stern, M. F. Folstein +12 more
Patients were all at the mild stage of disease at entry and were relatively comparable across sites, and features of the study cohort at baseline across sites are compared.
Archives of NeurologyIndividual Growth Curve Analysis of APOE ε4–Associated Cognitive Decline in Alzheimer Disease
86 Citations2005Brian Hoyt, Paul J. Massman +3 more
It seems that having 2 APOE e4 alleles is associated with a slower clinical course, consistent with hypotheses that the biological processes contributing to the onset of AD are different from those involved in determining its clinical course.
NeurologyApolipoprotein E epsilon 4 allele, cognitive decline, and deterioration of everyday performance in Alzheimer's disease
86 Citations1996Alexander Kurz, Rupert Egensperger +5 more
Journal of Neurology Neurosurgery & PsychiatryApolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease.
85 Citations1996Clive Holmes, Roy Levy +3 more
Neuroscience LettersApolipoprotein ϵ4 allele and disease progression in patients with late-onset Alzheimer's disease
84 Citations1995Hans Basun, M. Grut +2 more
It is indicated that the ϵ4 allele is associated with a better prognosis of the disease in late-onset AD but that there are probably factors other than theπ4 allele that are important for the AD phenotype.
Journal of Neurology Neurosurgery & PsychiatryLongitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism
67 Citations1998Maarit Lehtovirta, Jyrki T. Kuikka +6 more
Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer’s disease as the most severe cerebral hypoperfusion was found in the ε4 allele subgroups, which might have implications for therapeutic approaches in Alzheimer's disease.
Archives of NeurologyApolipoprotein E ϵ4 Allele and Familial Aggregation of Alzheimer Disease
67 Citations1998María Martínez, Dominique Campion +10 more
The hypothesis that the apoE epsilon4 allele enhances AD susceptibility, but putative factors enhancing risk for AD remain to be found is supported.
Neurology<i>APOE</i> genotype and survival in men and women with Alzheimer’s disease
65 Citations2002Gloria Dal Forno, Kathryn A. Carson +4 more
In this sample of mostly white, well-educated research participants with AD, the APOE &egr;4 allele was associated with shorter survival in men but not in women.
Neuroscience LettersApolipoprotein E4 accelerates dementia and increases cerebrospinal fluid tau levels in Alzheimer's disease
62 Citations1999Mitsuyasu Kanai, Masami Shizuka +5 more
The ApoE epsilon4 allele accelerates the progression of dementia and increases the levels of CSF tau in AD patients and in age-matched normal controls.
Dementia and Geriatric Cognitive DisordersApolipoprotein E ε4 Allele Differently Affects the Patterns of Neuropsychological Presentation in Early- and Late-Onset Alzheimer’s Disease Patients
59 Citations2004Camillo Marra, Alessandra Bizzarro +8 more
The 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 Ε3 allele carriers obtained worse performances in learning, long-term verbal memory and general intelligence tasks, while in LOAD patients, the pattern of cognitive impairment at the onset is not dependent on the possession of an Ε 4 allele in the genotype.
NeurologyFamilial Alzheimer disease in Latinos
59 Citations2006Gregory A. Rippon, Min Tang +4 more
APOE-ε4 and stroke independently increase risk of familial Alzheimer disease (AD) among Latinos, and may interact to further increase AD risk among women, and amongst women, the risk of AD associated with APOE- ε4 may be attenuated by a history of ERT.
Journal of NeurologyApolipoprotein E genotype and progression of Alzheimer's disease: the Rotterdam Study
56 Citations1999Arjen J. C. Slooter, Jeanine J. Houwing‐Duistermaat +7 more
It is found that the APOE*4 allele is not a strong determinant of survival in AD, and change in cognitive function and severity of dementia are similar for AD patients with and without APoe*4.
Journal of NeuropsychiatryAccelerated Memory Decline in Alzheimer's Disease With Apolipoprotein ϵ4 Allele
53 Citations2003Nobutsugu Hirono, Mamoru Hashimoto +3 more
Findings revealed that APOE epsilon4 allele is related to an accelerated memory decline in AD.
Archives of NeurologyApolipoprotein E ε4 and Age at Onset of Sporadic and Familial Alzheimer Disease in Caribbean Hispanics
45 Citations2006Lucia S. Olarte, Nicole Schupf +7 more
Apolipoprotein E e4 had a consistent lowering effect on age at onset of FAD, but this was attenuated in SAD, which suggests that among individuals with a family history of AD and the APOE e4 allele, additional genetic or environmental factors may accelerate the onset of dementia.
NeurologyApoE epsilon 4 allele and cognitive decline in patients with Alzheimer's disease
27 Citations1996Takashi Asada, Tetsuhiko Kariya +3 more
It is reported that no association of the apoE epsilon 4 allele with cognitive decline was found in AD subjects, and the relationship between apolipoprotein E alleles and the rate of cognitive decline in a longitudinal study of up to 3 years was examined.
Archives of NeurologyApolipoprotein E, Alzheimer Disease, and African Americans
27 Citations2003Richard Mayeux