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Cited by 1,366Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Preclinical Evidence of Alzheimer's Disease in Persons Homozygous for the ε4 Allele for Apolipoprotein E

Open access
Reiman, Eric M., Caselli, Richard J., Yun, Lang S., Chen, Kewei, Bandy, Daniel, Minoshima, Satoshi, Thibodeau, Stephen N., Osborne, David·1996·New England Journal of Medicine
DOI 10.1056/nejm199603213341202
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Abstract

BACKGROUND: Variants of the apolipoprotein E allele appear to account for most cases of late-onset Alzheimer's disease, and persons with two copies of the epsilon 4 allele appear to have an especially high risk of dementia. Positron-emission tomography (PET) has identified specific regions of the brain in which the rate of glucose metabolism declines progressively in patients with probable Alzheimer's disease. We used PET to investigate whether these same regions of the brain are affected in subjects homozygous for the epsilon 4 allele before the onset of cognitive impairment. METHODS: Apolipoprotein E genotypes were established in 235 volunteers 50 to 65 years of age who reported a family history of probable Alzheimer's disease. Neurologic and psychiatric evaluations, a battery of neuropsychological tests, magnetic resonance imaging, and PET were performed in 11 epsilon 4 homozygotes and 22 controls without the epsilon 4 allele who were matched for sex, age, and level of education. An automated method was used to generate an aggregate surface-projection map that compared regional rates of glucose metabolism in the two groups. RESULTS: The epsilon 4 homozygotes were cognitively normal. They had significantly reduced rates of glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as in previously studied patients with probable Alzheimer's disease. They also had reduced rates of glucose metabolism in additional prefrontal regions, which may be preferentially affected during normal aging. CONCLUSIONS: In late middle age, cognitively normal subjects who are homozygous for the epsilon 4 allele for apolipoprotein E have reduced glucose metabolism in the same regions of the brain as in patients with probable Alzheimer's disease. These findings provide preclinical evidence that the presence of the epsilon 4 allele is a risk factor for Alzheimer's disease. PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.

AI snapshot

Written from the paper’s full text.

TL;DR

In cognitively normal late-middle-aged ε4 homozygotes with a family history of probable Alzheimer's disease, PET showed reduced glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as in probable Alzheimer's disease, plus additional prefrontal reductions. These findings provide preclinical evidence that the ε4 allele is a risk factor for Alzheimer's disease and suggest PET may help test prevention therapies.

Key findings

  • Among 11 ε4 homozygotes and 22 non-ε4 controls matched for sex, age, and education, neuropsychological tests showed no significant differences in verbal memory, visual memory, naming, or visuospatial/constructional skills; MMSE scores were 29.4±0.8 vs. 29.8±0.6.
  • PET showed no significant whole-brain glucose metabolism difference (5.1±1.0 vs. 5.2±0.8 mg/min/100 g, P=0.62) or pontine difference (5.0±1.0 vs. 5.0±0.7, P=0.90), but ε4 homozygotes had significant bilateral reductions in the same posterior cingulate, parietal, temporal, and prefrontal regions as probable Alzheimer's disease; the text reports a maximal posterior cingulate z score of 8.26 (P<0.001), while Table 4 lists z=6.58 for posterior cingulate.
  • ε4 homozygotes also had significant reductions in additional prefrontal regions (maximal z=4.76, P<0.001 without correction for multiple comparisons), which the authors suggest may reflect accelerated aging.
  • One ε4 homozygote had neuropsychological evidence of mild cognitive impairment and the greatest metabolic reductions; excluding his data only minimally affected group means, and reductions remained.

Methods

  • Apolipoprotein E genotypes were established in 235 volunteers aged 50 to 65 who reported a family history of probable Alzheimer's disease in at least one first-degree relative; 12 ε4 homozygotes were identified, and 11 underwent imaging.
  • For each ε4 homozygote, 2 controls without the ε4 allele (6 ε2/ε3 and 16 ε3/ε3) were matched for sex, age within 3 years, and education within 2 years; subjects had neurologic and psychiatric evaluations, a neuropsychological battery, MRI, and FDG PET.
  • An automated three-dimensional stereotactic surface-projection algorithm compared regional glucose metabolism in ε4 homozygotes vs. controls and superimposed results on a prior probable-Alzheimer's disease map (37 patients vs. 22 normal controls); a critical z score of 4.32 identified voxels significant after correction for 278 resolution elements (P<0.05), with post hoc unpaired two-tailed t-tests.

Limitations

  • The paper states the findings should be considered preliminary; no attempt was made to address the combined effect of atrophy and partial-volume averaging on whole-brain or regional measurements.
  • The paper states that apolipoprotein E genotypes cannot predict whether or when Alzheimer's disease will develop, and that prospective longitudinal studies have not yet specified genotype-specific risks, onset ages, or attributable fractions; genotype-specific preventive therapies have not been identified.
  • Evident from the text: the imaging sample was small (11 ε4 homozygotes vs. 22 controls), the design was cross-sectional without longitudinal follow-up, and one ε4 homozygote had mild cognitive impairment and was excluded in a sensitivity analysis.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1056/nejm199603213341202

Cites

43 of 43 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 59 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The e4 homozygotes had significantly reduced rates of glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as previously studied patients with probable Alzheimer's disease.

    “They had significantly reduced rates of glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as in previously studied patients with probable Alzheimer's disease.”
    • Also stated in: § PET · plain
      “The group of e 4 homozygotes had significant bilateral reductions in glucose metabolism in the same posterior cingulate, parietal, temporal, and prefrontal regions as the group with probable Alzheimer's disease (Fig. 2 and Table 4)”
    • Also stated in: § DISCUSSION · plain
      “we found that the presymptomatic e4 homozygotes had significantly reduced rates of glucose metabolism in the same parietal, temporal, prefrontal, and posterior cingulate regions as patients with probable Alzheimer's disease.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cognitively normal e4 homozygotes in late middle age are in a presymptomatic stage of Alzheimer's disease.
  • Findingown data

    The e4 homozygotes also had reduced rates of glucose metabolism in additional prefrontal regions.

    “They also had reduced rates of glucose metabolism in additional prefrontal regions”
    • Also stated in: § PET · plain
      “The e4 homozygotes also had significant reductions in glucose metabolism in additional prefrontal regions (Fig. 2) (maximal z score, 4.76; PϽ0.001 without correction for multiple comparisons)”
    Quote in the paperSubstantial claim
  • Findingown data

    The e4 homozygotes were cognitively normal.

    “The e 4 homozygotes were cognitively normal.”
    Quote in the paperSubstantial claim
  • Findingown data

    Exclusion of the mild cognitive impairment subject's data only minimally affected the mean scores in the e4 homozygote group.

    “The exclusion of his data in a subsequent analysis only minimally affected the mean scores in the group of e 4 homozygotes.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The maximal reduction in glucose metabolism in the posterior cingulate cortex was significantly greater than those in the other regions (z score, 8.26; P<0.001).

    “the maximal reduction in glucose metabolism in the posterior cingulate cortex was significantly greater than those in the other regions (z score, 8.26; PϽ0.001).”
    Quote in the paperSubstantial claim
  • May combine two claims. 8
  • Classified as probably not a substantial claim. 15

  • May combine two claims.

    Findingown data

    There were no significant differences between e4 homozygotes and controls in verbal memory, visual memory, naming, or visuospatial and constructional skills.

    “There were no significant differences between groups in verbal memory (as measured by the Auditory Verbal Learning Test), visual memory (as measured by the recall portion of the Complex Figure Test), naming (as assessed by the Boston Naming Test), or visuospatial and constructional skills (as assessed by the copy portion of the Complex Figure Test and the Block Design subtest of the Wechsler Adult”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no significant differences between e4 homozygotes and controls in language skills, psychomotor speed, premorbid intellectual function, or directed attention span.

    “There were no significant differences in language skills or psychomotor speed (as measured by the Controlled Oral Word Association Test), estimates of premorbid intellectual function (as assessed by the Information subtest of the Wechsler Adult Intelligence Scale-Revised), or directed attention span (as assessed by the Digit Span subtest).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The metabolic reductions were greatest in an e4 homozygote with neuropsychological evidence of mild cognitive impairment, but were also apparent in the remaining, cognitively intact e4 homozygotes.

    “The metabolic reductions were greatest in an e4 homozygote with neuropsychological evidence of mild cognitive impairment, but were also apparent in the remaining, cognitively intact e4 homozygotes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisecitation

    Persons with two copies of the apolipoprotein E e4 allele (the e4/e4 genotype) have an especially high risk of Alzheimer's disease.

    “If, as case-control studies suggest, persons with two copies of the e 4 allele (the e 4/ e 4 genotype) have an especially high risk of Alzheimer's disease”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PET reveals abnormally low prefrontal and whole-brain glucose metabolism in more severely affected Alzheimer's disease patients.

    “abnormally low prefrontal and whole-brain levels in more severely affected patients”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] McGeer EG, 1990, Can J Neurol Sci source

      Not checked in the free run.

    • cites [10] Smith GS, 1992, Arch Neurol source

      Not checked in the free run.

    • cites [11] Mielke R, 1994, Dementia

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The apolipoprotein E e4 allele is harmful, increasing the risk of Alzheimer's disease and hastening the onset of dementia.

    “In contrast, the e 4 allele appears to be harmful, increasing the risk of Alzheimer's disease and hastening the onset of dementia.2,5”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] source

      Not checked in the free run.

    • cites [5] source

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  • Classified as probably not a substantial claim.

    Premisecitation

    PET reveals characteristic abnormalities in patients with probable and definite Alzheimer's disease, including abnormally low parietal, temporal, and posterior cingulate glucose metabolism.

    “When used to measure cerebral glucose metabolism, PET reveals characteristic abnormalities in patients with probable and definite Alzheimer's disease, including abnormally low parietal, temporal, and posterior cingulate levels”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] McGeer EG, 1990, Can J Neurol Sci source

      Not checked in the free run.

    • cites [10] Smith GS, 1992, Arch Neurol source

      Not checked in the free run.

    • cites [11] Mielke R, 1994, Dementia

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    PET reveals a progressive decline in glucose metabolism levels over time in Alzheimer's disease.

    “and a progressive decline in these levels over time.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] McGeer EG, 1990, Can J Neurol Sci source

      Not checked in the free run.

    • cites [10] Smith GS, 1992, Arch Neurol source

      Not checked in the free run.

    • cites [11] Mielke R, 1994, Dementia

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a recent study, subjects with the apolipoprotein E e3/e4 genotype, age-associated memory impairment, and a family history of Alzheimer's disease had abnormally low and asymmetric rates of glucose metabolism in a preselected parietal region before the onset of dementia.

    “In a recent study, subjects with the apolipoprotein E e 3/ e 4 genotype, age-associated memory impairment, and a family history of Alzheimer's disease had abnormally low and asymmetric rates of glucose metabolism in a preselected parietal region before the onset of dementia.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The additional prefrontal regions are preferentially affected during normal aging.

    “which PET, [29][30][31]32 and neuropathological studies 33 suggest are preferentially affected during normal aging.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [29] source

      Not checked in the free run.

    • cites [30] Salmon E, 1991, Acta Neurol Belg

      Not checked in the free run.

    • cites [31] Loessner A, 1995, J Nucl Med

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The pons appears to be the region least affected in patients with Alzheimer's disease.

    “Measurements in each voxel were normalized to that in the pons, which appears to be the region least affected in patients with Alzheimer's disease.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The posterior cingulate cortex is affected in Alzheimer's disease.

    “which is affected in Alzheimer's disease, 34,35”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] source

      Not checked in the free run.

    • cites [35] source

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  • May combine two claims.

    Study design and conductown data

    There were no significant differences between e4 homozygotes and controls in age, sex, handedness, years of education, age of the affected family member at onset of dementia, Hamilton Depression Rating Scale scores, or Mini-Mental State Examination scores.

    “There were no significant differences in age, sex, handedness, years of education, age of the affected family member at the onset of dementia, scores on the Hamilton Depression Rating Scale, or scores on the Mini-Mental State Examination (range, 28 to 30 in both groups).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    A critical z score of 4.32 was used to identify voxels with significant reductions in glucose metabolism after correction for the number of comparisons in the searched volume.

    “A critical z score of 4.32 was used to identify voxels in which the homozygous group had significant reductions in glucose metabolism in the same regions as the patients with probable Alzheimer's disease (P Ͻ 0.05 after correction for the number of comparisons [i.e., the 278 resolution elements] in the searched volume 28 ) as well as in additional regions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Investigators who obtained data were unaware of the subjects' apolipoprotein E genotypes.

    “Investigators who were unaware of the subjects' apolipoprotein E genotypes obtained data from medical and family histories, a neurologic examination, a structured psychiatric interview, 20 the Folstein modified Mini-Mental State Examination (MMSE), 21 the Hamilton Depression Rating Scale, 22 a battery of neuropsychological tests, and brain-imaging studies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The reductions in regional glucose metabolism could reflect decreased activity of terminal neuronal fields, decreased density of terminal neuronal fields, atrophy, or some combination of these factors.

    “Although the reductions in regional glucose metabolism could reflect decreased activity of terminal neuronal fields, 36 decreased density of terminal neuronal fields, atrophy, or some combination of these factors”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    For each of the 11 e4 homozygotes who participated in imaging, 2 control subjects without the e4 allele were matched for sex, age within three years, and level of education within two years.

    “For each of the 11 e 4 homozygotes who agreed to participate in the imaging studies, 2 control subjects without this allele (6 with the e 2/ e 3 genotype and 16 with the e 3/ e 3 genotype) were matched for sex, age (within three years), and level of education (within two years).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.

    “PET may offer a relatively rapid way of testing future treatments to prevent Alzheimer's disease.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The e4 allele is associated with an increased risk of coronary artery disease and fatal myocardial infarctions.

    “an increased risk of coronary artery disease and fatal myocardial infarctions, [41][42][43]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41][42][43]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The e2 allele is associated with a decreased risk of coronary artery disease, unless it is associated with type III hyperlipoproteinemia.

    “a decreased risk of coronary artery disease (unless it is associated with type III hyperlipoproteinemia), 42,43”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] source

      Not checked in the free run.

    • cites [43] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The e2 allele is associated with a decreased risk of Alzheimer's disease.

    “the e2 allele has been associated with a decreased risk of Alzheimer's disease, 4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4] source

      Not checked in the free run.

21 of 21

  • The paper relies on this without support.

    Cognitively normal e4 homozygotes in late middle age are in a presymptomatic stage of Alzheimer's disease.

    “we found that the presymptomatic e4 homozygotes had significantly reduced rates of glucose metabolism in the same parietal, temporal, prefrontal, and posterior cingulate regions as patients with probable Alzheimer's disease.”

  • The paper relies on this without support.

    Prospective, longitudinal studies of the general population have not yet specified the risk of Alzheimer's disease associated with each apolipoprotein E genotype, the mean age and variety of ages at the onset of dementia for each genotype, or the percentage of cases of Alzheimer's disease that are attributable to variants of the apolipoprotein E allele.

    “Prospective, longitudinal studies of the general population have not yet specified the risk of Alzheimer's disease associated with each apolipoprotein E genotype, the mean age and variety of ages at the onset of dementia for each genotype, or the percentage of cases of Alzheimer's disease that are attributable to variants of the apolipoprotein E allele.”

  • The paper relies on this without support.

    Genotype-specific preventive therapies have not yet been identified that might outweigh the psychological and social risks involved in making predictions about such a catastrophic illness.

    “Genotype-specific preventive therapies have not yet been identified that might outweigh the psychological and social risks involved in making predictions about such a catastrophic illness.”

  • The paper relies on this without support.

    The association between the e4 allele and Alzheimer's disease has been observed internationally in about 100 clinics.

    “an association that has now been observed internationally in about 100 clinics.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The brains of APOE4 carriers display decreased glucose utilization in numerous AD-relevant brain regions, as observed by FDG-PET.

    “As shown in previous studies, the brains of APOE4 carriers display decreased glucose utilization in numerous AD-relevant brain regions, as observed by FDG-PET16–18.”

    From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [16]

    The PET and Discussion passages report reduced glucose metabolism in posterior cingulate, parietal, temporal, and prefrontal regions associated with Alzheimer's disease. The study's comparison, however, was of ε4 homozygotes against noncarriers; it does not establish the same pattern for APOE4 carriers generally. Page numbers are not available in the supplied passages. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Both young and old APOE4 carriers display decreased glucose utilization, measured by FDG-PET, in brain regions similar to those seen with AD patients.

    “early reports by Reiman and colleagues demonstrated that both young and old APOE4 carriers display decreased glucose utilization, as measured by fluorodeoxyglucose positron emission tomography (FDG-PET), in brain regions similar to those seen with AD patients16–18.”

    From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [16]

    The PET results and Discussion report reduced glucose metabolism in APOE ε4 homozygotes in the same regions affected in patients with probable Alzheimer’s disease; the Brain Imaging section specifies that the PET scans used fluorodeoxyglucose. But this study examined carriers aged 50–65, not both young and old carriers, and its findings concern people with two ε4 alleles rather than APOE4 carriers generally. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Young, cognitively normal apoE4 carriers have glucose hypometabolism in brain regions affected by Alzheimer's disease.

    “Young, cognitively normal apoE4 carriers have glucose hypometabolism in brain regions affected by AD [29–31]”

    From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [29]

    The Abstract reports reduced glucose metabolism in Alzheimer’s-affected brain regions among cognitively normal ε4 homozygotes. But its Methods specify volunteers aged 50–65, and Figure 2 gives a mean age of 55; this does not establish the claim for young carriers or for carriers generally. Page numbers are not supplied in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • FDG-PET imaging shows hypometabolism in Alzheimer's disease brains, mainly in the temporoparietal cortex including the precuneus and posterior cingulate cortex.

    “[18F] fluorodeoxyglucose (FDG)-PET imaging showed hypometabolism in AD brains, mainly in the temporoparietal cortex including the precuneus and posterior cingulate cortex (Reiman et al., 1996; Foster et al., 2007).”

    From APOE genotype-dependent differences in human astrocytic energy metabolism (2025) · cites this paper as Reiman et al., 1996

    The Figure 1 description (Discussion; page unavailable) reports reduced glucose metabolism in patients with probable Alzheimer’s disease in bilateral parietal, temporal, posterior cingulate, and prefrontal regions. The paper does not identify the precuneus or establish that hypometabolism was mainly temporoparietal, so those details are not supported by this source. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • APOE4 is associated with increased Aβ deposition, but its influence on metabolic pathways may contribute to AD risk independently of Aβ.

    “As such, APOE4 is associated with increased Aβ deposition but accumulating evidence suggests that its influence on metabolic pathways may contribute to disease risk independently of Aβ [3][4][5][6][7] .”

    From APOE4-drives brain bioenergetic shifts independent of Alzheimer’s disease pathology (2026) · cites this paper as [4]

    The Discussion (page not provided) associates the ε4 allele with faster β-amyloid deposition, and the Abstract reports reduced brain glucose metabolism in cognitively normal ε4 homozygotes. The paper does not establish that the metabolic difference contributes to Alzheimer’s disease risk independently of amyloid deposition. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 11

  1. Roses AD, 1995, J NIH Res, 7, 51
  2. Mielke R, 1994, Dementia, 5, 36
  3. Minoshima S, 1995, J Nucl Med, 36, 1238
  4. Pietrini P, 1993, Dementia, 4, 94
  5. Spitzer RL, Williams JBW, Gibbon M, First MD. User's guide for the structured clinical interview for DSM-III-R (SCID). Washington, D.C.: American Psychiatric Press, 1990.
  6. Minoshima S, 1994, J Nucl Med, 35, 1528
  7. Salmon E, 1991, Acta Neurol Belg, 91, 288
  8. Loessner A, 1995, J Nucl Med, 36, 1141
  9. Davignon J, 1987, Trans Am Clin Climatol Assoc, 99, 100
  10. Wisniewski T, 1994, Am J Pathol, 145, 1030
  11. Kaplitt MG, 1995, Abstr Soc Neurosci, 21, 1008

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Authors
Reiman, E. M., Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., & Osborne, D.
Affiliations
  • University of Arizona (US)
  • Mayo Clinic in Arizona (US)
  • University of Michigan (US)
  • Mayo Clinic (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1996-03-21
Volume
334
Issue
12
Pages
752-758
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199603213341202
OpenAlex
W2023121717
Semantic Scholar
a04d6dd3638573927f661225155d8ef1ee0fff4d
Cited by
1,366
References
43
Citations by year
2026: 15 · 2025: 10 · 2024: 20 · 2023: 28 · 2022: 28 · 2021: 27 · 2020: 30 · 2019: 30 · 2018: 40 · 2017: 41 · 2016: 42 · 2015: 37 · 2014: 53 · 2013: 56 · 2012: 64
FWCI
42.63
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Academy of Neurology
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, apolipoprotein E, ε4 allele, homozygosity, preclinical Alzheimer's disease, glucose metabolism, positron emission tomography, brain glucose hypometabolism, family history of Alzheimer's disease, prefrontal cortex, posterior cingulate cortex, parietal cortex, temporal cortex, normal aging, genetic risk factors
MeSH terms
Aged, Alleles, Alzheimer Disease, Apolipoproteins E, Brain, Female, Genotype, Glucose, Homozygote, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Neuropsychological Tests, Tomography, Emission-Computed, Case-Control Studies

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