Age-associated memory impairment (AAMI) is a clinical entity which was originally described to define memory problems linked to normal aging. Apolipoprotein E and ACE genes have both been associated ...with cognitive impairment in aging and dementia. The purpose of this study was to investigate memory and executive functions in AAMI according to the genetic background. We found that subjects carrying the Apo E epsilon4 allele exhibit lower memory performance on tests of both declarative and procedural memory. We did not find differences on frontal lobe tests. These findings give further support to the hypothesis concerning a genetic susceptibility for cognitive impairment in aging.
Most cases of early-onset Alzheimer's disease (EOAD) are sporadic. A minority of EOAD are caused by specific genetic defects in PSEN1, PSEN2, or AβPP genes. Magnetic resonance imaging (MRI) and ...cerebrospinal fluid (CSF) biomarker comparisons between sporadic and monogenic EOAD are practically inexistent. CSF and MRI data from 14 amnestic-onset sporadic EOAD (sEOAD) subjects were compared with data from 8 symptomatic PSEN1 mutation carriers (PSEN1) and 14 age-matched cognitively-preserved controls. CSF concentrations of amyloid-β (Aβ)(42), total tau (t-tau), and phosphorylated tau (p-tau) were determined. Cortical thickness (CTh) and grey matter loss were compared between groups and correlated with CSF biomarkers. PSEN1 had significantly lower CSF Aβ(42) levels compared to sEOAD (mean 244.8 pg/ml versus 381.4 pg/ml; p = 0.006), but no differences in t-tau or p-tau. Both sEOAD and PSEN1 showed widespread CTh loss in AD target areas when compared with controls. No differences were found in the direct comparison between sEOAD and PSEN1 CTh after adjusting for age and Mini-Mental Status Examination scores. Neither was a correlation found between Aβ(42) levels and CTh. CTh in the left superior parietal and caudal middle frontal areas was negatively correlated with t-tau values. In conclusion, PSEN1 had lower Aβ(42) CSF levels compared with sEOAD, suggesting a greater cerebral deposition of Aβ(42). These differences in Aβ(42) deposition were not significantly reflected in the brain structure, and CTh was only correlated with total tau. The lack of significant differences in relation to t-tau and p-tau levels and to the severity of CTh or grey matter loss suggests a similar level of neuronal injury despite higher Aβ(42) load in PSEN1.
We investigated the relationship among neuroanatomical, neurochemical and genetic variables in 44 subjects with age-related memory impairment. Hydrogen magnetic resonance spectroscopy was used to ...determine N-acetyl/creatine (NAA/Cr) concentrations in basal ganglia and medial temporal regions. Volumetric measures were obtained for caudate nucleus and hippocampus. Genetic polymorphisms examined included apolipoproteins (APO) E and CI, angiotensin converting enzyme and dopamine D2 receptor TaqI genes. Age was found to be negatively correlated with hippocampal and basal ganglia volumes, but not with neurochemical values. Multiple regression analyses showed that the APOC1 polymorphism was the only variable which predicted NAA/Cr values in basal ganglia. NAA/Cr metabolites in the medial temporal lobe but not in the basal ganglia region were related with lower performance in verbal memory.
Introduction - Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology in order to minimize clinical manifestations. Previous studies showed that CR modulates the patterns ...of brain activity in both healthy and clinical populations. In the present study we sought to determine whether reorganizations of functional brain resources linked to CR could already be observed in amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD) patients when performing a task corresponding to an unaffected cognitive domain. We further investigated if activity in regions showing task-induced deactivations, usually identified as pertaining to the default-mode network (DMN), was also influenced by CR. Methods - Fifteen healthy elders, 15 a-MCI and 15 AD patients underwent functional magnetic resonance imaging (fMRI) during a speech comprehension task. Differences in the regression of slopes between CR proxies and blood-oxygen-level dependent (BOLD) signals across clinical groups were investigated for activation and deactivation areas. Correlations between significant fMRI results and a language comprehension test were also computed. Results - Among a-MCI and AD we observed positive correlations between CR measures and BOLD signals in task-induced activation areas directly processing speech, as well as greater deactivations in regions of the DMN. These relationships were inverted in healthy elders. We found no evidence that these results were mediated by gray matter volumes. Increased activity in left frontal areas and decreased activity in the anterior cingulate were related to better language comprehension in clinical evaluations. Conclusions - The present findings provide evidence that the neurofunctional reorganizations related to CR among a-MCI and AD patients can be seen even when considering a preserved cognitive domain, being independent of gray matter atrophy. Areas showing both task-induced activations and deactivations are modulated by CR in an opposite manner when considering healthy elders versus patients. Brain reorganizations facilitated by CR may reflect behavioral compensatory mechanisms.
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