Extent of hippocampal atrophy predicts degree of deficit in recall.
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ABSTRACT:
SUBMITTER: Patai EZ
PROVIDER: S-EPMC4611643 | biostudies-other | 2015 Oct
REPOSITORIES: biostudies-other
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Project description:Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximately 20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.
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Project description:IntroductionUnderstanding relationships among blood pressure (BP), cognition, and brain volume could inform Alzheimer's disease (AD) management.MethodsWe investigated Alzheimer's Disease Neuroimaging Initiative (ADNI) participants: 200 controls, 346 mild cognitive impairment (MCI), and 154 AD. National Alzheimer's Co-ordinating Center (NACC) participants were separately analyzed: 1098 controls, 2297 MCI, and 4845 AD. Relationships between cognition and BP were assessed in both cohorts and BP and atrophy rates in ADNI. Multivariate mixed linear-regression models were fitted with joint outcomes of BP (systolic, diastolic, and pulse pressure), cognition (Mini-Mental State Examination, Logical Memory, and Digit Symbol) and atrophy rate (whole-brain, hippocampus).ResultsADNI MCI and AD patients with greater baseline systolic BP had higher hippocampal atrophy rates ([r, P value]; 0.2, 0.005 and 0.2, 0.04, respectively). NACC AD patients with lower systolic BP had lower cognitive scores (0.1, 0.0003).DiscussionHigher late-life BP may be associated with faster decline in cognitively impaired elders.
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Project description:IntroductionAsymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.MethodsWe created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.ResultsOur risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset.DiscussionIndividualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.
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Project description:ObjectiveTo 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.MethodsParticipants were cognitively healthy adults with (FH+) (n = 60) and without (FH-) (n = 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.ResultsNeither FH nor APOE4 had an effect on regional GM or cognition at baseline. Longitudinally, a FH × APOE4 interaction was found in the right posterior hippocampus, which was driven by a significant difference between the FH+ and FH- subjects who were APOE4-. 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.ConclusionOver 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.
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Project description:BACKGROUND:The UNC5C rs3846455G allele has been linked to poor cognitive resilience against age-related neuropathologies, but this association remains to be replicated, and the allele's effect on hippocampal neurodegeneration needs to be examined. OBJECTIVE:To further validate the association between rs3846455G and faster cognitive decline, especially among cognitively normal older adults, and to assess whether rs3846455G predicts accelerated hippocampal volume loss in older adults. METHODS:We assessed participants in the Harvard Aging Brain Study (HABS), a longitudinal cohort study of older adults who were clinically normal at baseline. To avoid bias from population admixture, analyses were limited to participants of European descent with longitudinal neuroimaging data (n?=?174). Linear mixed effect models were used to examine the effect of rs3846455G on longitudinal change of the Preclinical Alzheimer Cognitive Composite (PACC) and MRI-measured bilateral hippocampal volume, adjusting for baseline amyloid-? (A?) measured by the cortical Pittsburgh Compound B PET distributed volume ratio. We also tested whether hippocampal atrophy mediates the association between rs3846455G and greater PACC decline through a mediation analysis. RESULTS:rs3846455G was associated with greater PACC decline (?=?-0.087/year, 95% CI -0.169 to -0.005, p?=?0.039) after controlling for baseline A?. Further, rs3846455G predicted accelerated hippocampal atrophy after controlling for baseline A? (?=?-57.3 mm3/year, 95% CI -102.8 to -11.9, p?=?0.014). The association between rs3846455G and greater PACC decline was partially mediated by accelerated hippocampal atrophy (mediated effect (relative scale)?=?-0.014, 95% CI -0.032 to -6.0×10-4, p?=?0.039). CONCLUSION:UNC5C rs3846455G predicts greater cognitive decline and accelerated hippocampal atrophy in clinically normal older adults.
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