Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease

Honea, Robyn A.; Swerdlow, Russell H.; Vidoni, Eric D.; Burns, Jeffrey M.

doi:10.1212/wnl.0b013e31820e7b74

Cited by 93 publications

(94 citation statements)

References 39 publications

(47 reference statements)

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“…The relative consistency of these FH findings across diverse neuroimaging modalities 4,[7][8][9]11 suggests that FH is a prominent, even if nonspecific, risk factor for AD perhaps embodying an array of genetic and environmental indices that remain to be fully elucidated. 10,22 Contrary to prior reports suggesting that maternal history of AD might confer a greater risk of ADrelated cerebral abnormalities than paternal history of AD, 5,7,8,18,23 we found that pFHϩ subjects were just as likely as mFHϩ subjects to experience atrophy of the posterior hippocampus. This observation suggests that, in our cohort, the FH effect was not driven by a particular parent of origin.…”

Section: Results Demographic Findingscontrasting

confidence: 99%

“…For example, recent cross-sectional 18 and longitudinal 5 studies have found evidence for GM volume reductions in AD-susceptible brain regions, such as the precuneus, among cognitively intact FHϩ individuals relative to FHϪ peers. Our study extends these findings 5,18 by using a considerably larger sample, implementing a longer follow-up, and, more importantly, showing that FH-related hippocampal atrophy is present at a relatively young age (our cohort's mean baseline age was 54 years). The relative consistency of these FH findings across diverse neuroimaging modalities 4,[7][8][9]11 suggests that FH is a prominent, even if nonspecific, risk factor for AD perhaps embodying an array of genetic and environmental indices that remain to be fully elucidated.…”

Section: Results Demographic Findingssupporting

confidence: 75%

“…To determine whether maternal history of AD had a differential effect on GM atrophy than paternal history of AD, 5,8 we repeated the longitudinal analysis described above but this time using a one-way ANCOVA design to assess whether there was a parent of origin effect on participants' 4-year follow-up scans, while adjusting for age, sex, baseline voxel-wise GM, and APOE4 status (see Results section for specific a priori contrasts tested). For all the imaging analyses described above, only clusters with a minimum of 188 continuous voxels and p voxel Ͻ 0.005 were deemed significant.…”

Section: Standard Protocol Approvals Registrations and Patient Consmentioning

confidence: 99%

“…In the present article, we extend these prior findings by investigating the longitudinal effect of FH and APOE4 on brain morphometry within this cohort, with a particular focus on temporoparietal regions that are now known to be vulnerable to AD pathology. 16,17 In addition, because it has recently been shown that the sex of the ADaffected parent may be influential, with maternal FH being more deleterious, 5,7,8,18 we conducted supplementary analyses to determine whether any observed FH effects were possibly driven by maternal FH. In parallel analyses, we also investigated the effect of FH and APOE4 on cognitive decline.…”

mentioning

confidence: 99%

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Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Okonkwo¹,

Xu²,

Dowling³

et al. 2012

Neurology

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Objective: To evaluate the longitudinal influence of family history (FH) of Alzheimer disease (AD) and apolipoprotein E ⑀4 allele (APOE4) on brain atrophy and cognitive decline over 4 years among asymptomatic middle-aged individuals.Methods: Participants were cognitively healthy adults with (FHϩ) (n ϭ 60) and without (FHϪ) (n ϭ 48) a FH of AD (mean age at baseline 54 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention. They underwent APOE genotyping, cognitive testing, and an MRI scan at baseline and 4 years later. A covariate-adjusted voxel-based analysis interrogated gray matter (GM) modulated probability maps at the 4-year follow-up visit as a function of FH and APOE4. We also examined the influence of parent of origin on GM atrophy. Parallel analyses investigated the effects of FH and APOE4 on cognitive decline.Results: Neither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH ϫ APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FHϩ and FHϪ subjects who were APOE4Ϫ. In addition, a significant FH main effect was observed in the left posterior hippocampus. No significant APOE4 main effects were detected. Persons with a maternal history of AD were just as likely as those with a paternal history of AD to experience posterior hippocampal atrophy. There was no longitudinal decline in cognition within the cohort. Conclusion:Over a 4-year interval, asymptomatic middle-aged adults with FH of AD exhibit significant atrophy in the posterior hippocampi in the absence of measurable cognitive changes. This result provides further evidence that detectable disease-related neuroanatomic changes do occur early in the AD pathologic cascade. Neurology ® 2012;78:1769-1776 GLOSSARY AD ϭ Alzheimer disease; ANCOVA ϭ analysis of covariance; FH ϭ family history; GM ϭ gray matter; mFH ϭ maternal family history; MNI ϭ Montreal Neurological Institute; pFH ϭ paternal family history; WRAP ϭ Wisconsin Registry for Alzheimer's Prevention.

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Section: Results Demographic Findingscontrasting

confidence: 99%

Section: Results Demographic Findingssupporting

confidence: 75%

Section: Standard Protocol Approvals Registrations and Patient Consmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Okonkwo¹,

Xu²,

Dowling³

et al. 2012

Neurology

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“…It remains to be established whether Ab accumulation is also an early event in LOAD. 1 Previous brain imaging studies have shown that, among NL individuals who have parents with LOAD, those with maternal FH (FHm) present with increased Ab load on 11 C-Pittsburgh compound B (PiB)-PET, 11,12 progressive glucose metabolism reductions on 18 F-fluoro-2-deoxyglucose (FDG)-PET, 13,14 and gray matter volume (GMV) loss on MRI [15][16][17][18] in the same regions as those with clinical AD. In contrast, NL individuals with paternal FH (FHp) are far less likely to show biomarker abnormalities.…”

mentioning

confidence: 99%

Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD

et al. 2014

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Objectives: This brain imaging study examines whether cognitively normal (NL) individuals with 2 parents affected by late-onset Alzheimer disease (LOAD) show evidence of more extensive Alzheimer disease pathology compared with those who have a single parent affected by LOAD.Methods: Fifty-two NL individuals received MRI, 11 C-Pittsburgh compound B (PiB)-PET, and 18 F-fluoro-2-deoxyglucose (FDG)-PET. These included 4 demographically balanced groups (n 5 13/group, aged 32-72 years, 60% female, 30% APOE e4 carriers) of NL individuals with maternal (FHm), paternal (FHp), and maternal and paternal (FHmp) family history of LOAD, and with negative family history (FH2). Statistical parametric mapping, voxel-based morphometry, and z-score mapping were used to compare MRI gray matter volumes (GMVs), partial volumecorrected PiB retention, and FDG metabolism across FH groups and vs FH2. Alzheimer disease (AD) is an age-related neurodegenerative disease and the most common form of dementia. Clinical studies indicate that by the time patients seek diagnosis, the amount of irreversible brain damage that may have already occurred hinders treatment potential. Effective interventions, as they become available, ideally would be implemented in at-risk individuals before symptoms occur.Having a family history (FH) of AD is a major risk factor for developing the disease. 1,2 While the rare early-onset forms of AD (EOAD) have autosomal dominant genetic inheritance, the risk of developing late-onset AD (LOAD) (i.e., .99% of the AD population older than 60 years) is influenced by genetic and nongenetic factors.1 Although LOAD does not show recognizable mendelian inheritance, risk is to some extent genetically determined, as shown by the familial aggregation of many cases.2 Among probands, those with a parent affected by LOAD are at particularly high risk, 3,4 and the risk is higher still when both parents are affected. [5][6][7] However, because only ,5% of individuals have both parents affected by LOAD, 2,5-7 the clinical profile associated with this rare circumstance has been poorly studied and epidemiologic findings have not been characterized by the use of biomarkers.

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Association of Acquired and Heritable Factors With Intergenerational Differences in Age at Symptomatic Onset of Alzheimer Disease Between Offspring and Parents With Dementia

et al. 2019

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Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease

Cited by 93 publications

References 39 publications

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Family history of Alzheimer disease predicts hippocampal atrophy in healthy middle-aged adults

Brain imaging of cognitively normal individuals with 2 parents affected by late-onset AD

Association of Acquired and Heritable Factors With Intergenerational Differences in Age at Symptomatic Onset of Alzheimer Disease Between Offspring and Parents With Dementia

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