Dataset Information

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline.

ABSTRACT:

Objective

To test the hypothesis that higher neuronal density in brainstem aminergic nuclei contributes to neural reserve.

Methods

Participants are 165 individuals from the Rush Memory and Aging Project, a longitudinal clinical-pathologic cohort study. They completed a mean of 5.8 years of annual evaluations that included a battery of 19 cognitive tests from which a previously established composite measure of global cognition was derived. Upon death, they had a brain autopsy and uniform neuropathologic examination that provided estimates of the density of aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area plus summary measures of neuronal neurofibrillary tangles and Lewy bodies from these nuclei and medial temporal lobe and neocortex.

Results

Neuronal densities in each nucleus were approximately normally distributed. In separate analyses, higher neuronal density in each nucleus except the ventral tegmental area was associated with slower rate of cognitive decline, but when modeled together only locus ceruleus neuronal density was related to cognitive decline (estimate = 0.003, SE = 0.001, p < 0.001). Higher densities of tangles and Lewy bodies in these brainstem nuclei were associated with faster cognitive decline even after controlling for pathologic burden elsewhere in the brain. Locus ceruleus neuronal density, brainstem tangles, and brainstem Lewy bodies had independent associations with rate of cognitive decline. In addition, at higher levels of locus ceruleus neuronal density, the association of Lewy bodies with cognitive decline was diminished.

Conclusion

Density of noradrenergic neurons in the locus ceruleus may be a structural component of neural reserve.

SUBMITTER: Wilson RS

PROVIDER: S-EPMC3691778 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveBased on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time.MethodsForty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression.ResultsPatients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ?p (2) = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ?p (2) = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ?p (2) = 0.126) and memory (p = 0.037, ?p (2) = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment.ConclusionWe provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS.

Project description:BackgroundThe relative importance of different components of cognitive reserve (CR), as well as their differences by gender, are poorly established.ObjectiveTo explore several dimensions of CR, their differences by gender, and their effects on cognitive performance and trajectory in a cohort of older people without relevant psychiatric, neurologic, or systemic conditions.MethodsTwenty-one variables related to the education, occupation, social activities, and life habits of 1,093 home-dwelling and cognitively healthy individuals, between 68 and 86 years old, were explored using factorial analyses to delineate several dimensions of CR. These dimensions were contrasted with baseline cognitive performance, follow-up over 5 years of participants' cognitive trajectory, conversion to mild cognitive impairment (MCI), and brain volumes using regression and growth curve models, controlling for gender, age, marital status, number of medications, trait anxiety, depression, and ApoE genotype.ResultsFive highly intercorrelated dimensions of CR were identified, with some differences in their structure and effects based on gender. Three of them, education/occupation, midlife cognitive activities, and leisure activities, were significantly associated with late-life cognitive performance, accounting for more than 20% of its variance. The education/occupation had positive effect on the rate of cognitive decline during the 5-year follow up in individuals with final diagnosis of MCI but showed a reduced risk for MCI in men. None of these dimensions showed significant relationships with gray or white matter volumes.ConclusionProxy markers of CR can be represented by five interrelated dimensions. Education/occupation, midlife cognitive activities, and leisure activities are associated with better cognitive performance in old age and provide a buffer against cognitive impairment. Education/occupation may delay the clinical onset of MCI and is also associated with the rate of change in cognitive performance.