To examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metabolism in elderly cognitively healthy (HC) subjects with preclinical Alzheimer disease (AD).
Fifty-two HC subjects (mean age 75 years) with FDG-PET and CSF measurement of Aβ1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Aβ1-42 was <192 pg/mL (Aβ1-42 [+]) vs HC with normal Aβ (Aβ1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Aβ1-42 status (Aβ1-42 [+] vs Aβ1-42 [-]) on FDG-PET metabolism in regions of interest (ROIs) (posterior cingulate, angular gyrus, inferior/middle temporal gyrus) and the whole brain (voxel-based).
An interaction between education and CSF Aβ1-42 status was observed for FDG-PET in the posterior cingulate (p < 0.001) and angular gyrus ROIs (p = 0.03), but was not significant for the inferior/middle temporal gyrus ROI (p = 0.06), controlled for age, sex, and global cognitive ability (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the Aβ1-42 (+) group, but with higher FDG-PET in the Aβ1-42 (-) group. Voxel-based analysis showed that this interaction effect was primarily restricted to temporo-parietal and ventral prefrontal brain areas.
Higher education was associated with lower FDG-PET in preclinical AD (Aβ1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism.
"A number of epidemiological studies have confirmed that patients with higher CR can tolerate more AD pathology than those with low reserve, while presenting with similar clinical symptoms. These conclusions are also supported by evidence from positron emission tomography (PET) studies, indicating an inverse relationship between regional cerebral glucose metabolism and years of education, not only in patients with AD but also with other forms of dementia    . Using structural MRI, we have recently shown in a large cohort of AD and MCI patients that, despite a similar cognitive decline, individuals with a higher level of education exhibit more grey matter (GM) atrophy than those with a lower educational level in brain regions typically targeted by AD pathology (i.e., medial temporal lobes) . "
[Show abstract][Hide abstract] ABSTRACT: One factor believed to impact brain resilience to the pathological damage of Alzheimer's disease (AD) is the so-called "cognitive reserve" (CR). A critical issue that still needs to be fully understood is the mechanism by which environmental enrichment interacts with brain plasticity to determine resilience to AD pathology. Previous work using PET suggests that increased brain connectivity might be at the origin of the compensatory mechanisms implicated in this process. This study aims to further clarify this issue using resting-state functional MRI. Resting-state functional MRI was collected for 11 patients with AD, 18 with mild cognitive impairment (MCI), and 16 healthy controls, and analyzed to isolate the default mode network (DMN). A quantitative score of CR was obtained by combining information about number of years of education and type of schools attended. Consistent with previous reports, education was found to modulate functional connectivity in the posterior cingulate cortex, whose disconnection with the temporal lobes is known to be critical for the conversion from MCI to AD. This effect was highly significant in AD patients, less so in patients with MCI, and absent in healthy subjects. These findings show the potential neural mechanisms underlying the individual's ability to cope with brain damage, although they should be treated with some caution based on small numbers.
"Therefore, new AD hypothesis have emerged to conciliate these phenomena. Recently, the involvement of the brain cognitive reserve in the development of this pathology has gained a renewed interest (Stern, 2012; Ewers et al., 2013; Lo et al., 2013). Furthermore, systemic inflammation may induce neuroinflammation that impairs some key elements of the cognitive reserve (neurogenesis or synaptic plasticity) and has been directly related to AD and even suggested to trigger this pathology (Herrup, 2010). "
[Show abstract][Hide abstract] ABSTRACT: The cognitive reserve is the capacity of the brain to maintain normal performance while exposed to insults or ageing. Increasing evidences point to a role for the interaction between inflammatory conditions and cognitive reserve status during Alzheimer's disease (AD) progression. The production of new neurons along adult life can be considered as one of the components of the cognitive reserve. Interestingly, adult neurogenesis is decreased in mouse models of AD and following inflammatory processes. The aim of this work is to reveal the long-term impact of a systemic inflammatory event on memory and adult neurogenesis in wild type (WT) and triple transgenic mouse model of AD (3xTg-AD). Four month-old mice were intraperitoneally injected once with saline or lipopolysaccharide (LPS) and their performance on spatial memory analyzed with the Morris water maze (MWM) test 7 weeks later. Our data showed that a single intraperitoneal injection with LPS has a long-term impact in the production of hippocampal neurons. Consistently, LPS-treated WT mice showed less doublecortin-positive neurons, less synaptic contacts in newborn neurons, and decreased dendritic volume and complexity. These surprising observations were accompanied with memory deficits. 3xTg-AD mice showed a decrease in new neurons in the dentate gyrus compatible with, although exacerbated, the pattern observed in WT LPS-treated mice. In 3xTg-AD mice, LPS injection did not significantly affected the production of new neurons but reduced their number of synaptic puncta and impaired memory performance, when compared to the observations made in saline-treated 3xTg-AD mice. These data indicate that LPS treatment induces a long-term impairment on hippocampal neurogenesis and memory. Our results show that acute neuroinflammatory events influence the production of new hippocampal neurons, affecting the cognitive reserve and leading to the development of memory deficits associated to AD pathology.
Frontiers in Neuroscience 04/2014; 8(8):83. DOI:10.3389/fnins.2014.00083 · 3.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: "Reserve" hypotheses in neurodegenerative disease are theoretical concepts that attempt to explain how some individuals are able to maintain normal cognition despite pathologic disease burden sufficient to cause cognitive decline or overt dementia in others.(1) This idea was born out of the seminal work of Katzman et al.(2) who described, at postmortem, a subset of older individuals with preserved cognition who harbored substantial levels of neocortical plaques. To explain this disconnect between pathologic burden and clinical state, 2 "reserve" terms have been proposed. Brain reserve refers to intrinsic differences in brain structure or neuronal capacity and is measured by assessment of brain volume and by postmortem assessment of synaptic density and neuronal number or size.(1,3) Cognitive reserve, on the other hand, refers to differences in how individuals utilize adaptive cognitive strategies and engage neural networks to maintain normal cognition in the face of pathologic burden.(1) Cognitive reserve is traditionally measured by surrogate markers, such as overall ability level, and lifestyle factors, such as education, occupation, and cognitive, social, and physical leisure activities.(4) With the advent of in vivo antemortem biomarkers of Alzheimer disease (AD) that allow us to quantify brain structure, function, and molecular composition, we now know that approximately 30% of elderly individuals with no clinical impairment have evidence for preclinical AD (pAD), indicated by abnormal Aβ levels by imaging or CSF analysis.(1,5) As the field moves toward preclinical diagnosis and eventual treatment of individuals with pAD, it is critical that we understand the mediating factors of the relationships among cognition, function, and pathologic burden.(6) One potential mediating factor is the influence of cognitive and brain reserve.
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