Dataset Information

Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology.

ABSTRACT:

Objective

To determine whether asymptomatic persons with Alzheimer disease (AD) neuropathologic change differ in the trajectory of their cognitive performance compared to asymptomatic persons without AD neuropathologic change.

Methods

Longitudinal performance on standard neuropsychological tests was examined in participants who died within 2 years of their last cognitive assessment and who were never diagnosed with mild cognitive impairment or dementia (Clinical Dementia Rating global score of 0 at all assessments). Using cognitive and neuropathologic data collected between 2005 and 2013 from the 34 National Institute on Aging-sponsored Alzheimer's Disease Centers, cognitive trajectories were compared for persons with and without evidence of AD neuropathologic change. We evaluated rates of decline in 4 domains (episodic memory, language, attention/working memory, executive function). The significance of the differences (?) in rates of decline was tested using linear regression, adjusting for age, education, sex, and other neuropathologic lesions.

Results

Participants who had low to high levels of AD neuropathologic change (n = 131) showed a greater rate of decline on the attention/working memory domain score (? = -0.11; 95% confidence interval = -0.19, -0.02; p = 0.02) when compared to 80 participants who died without evidence of AD neuropathologic change.

Conclusions

Clinically normal individuals who come to autopsy with AD neuropathologic change exhibit subtle evidence of declining cognitive trajectories for attention/working memory.

SUBMITTER: Monsell SE

PROVIDER: S-EPMC4132573 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology.

Monsell Sarah E SE Mock Charles C Hassenstab Jason J Roe Catherine M CM Cairns Nigel J NJ Morris John C JC Kukull Walter W

Neurology 20140620 5

<h4>Objective</h4>To determine whether asymptomatic persons with Alzheimer disease (AD) neuropathologic change differ in the trajectory of their cognitive performance compared to asymptomatic persons without AD neuropathologic change.<h4>Methods</h4>Longitudinal performance on standard neuropsychological tests was examined in participants who died within 2 years of their last cognitive assessment and who were never diagnosed with mild cognitive impairment or dementia (Clinical Dementia Rating gl ...[more]

PMID: 24951474

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Project description:Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Abeta peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Abeta peptide, similar but not identical to the Abeta peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Abeta, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Abeta 42 levels, except for the Arctic mutation, which alters the Abeta sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Abeta deposition in most mouse lines. Doubly (APP x mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Abeta. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Abeta in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Abeta oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau -/- background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Abeta or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis.

Project description:Importance:Social determinants of health, such as income, education, housing quality, and employment, are associated with disparities in Alzheimer disease and health generally, yet these determinants are rarely incorporated within neuropathology research. Objective:To establish the feasibility of linking neuropathology data to social determinants of health exposures using neighborhood disadvantage metrics (the validated Area Deprivation Index) and to evaluate the association between neighborhood disadvantage and Alzheimer disease-related neuropathology. Design, Setting, and Participants:This cross-sectional study consisted of decedents with a known home address who donated their brains to 1 of 2 Alzheimer disease research center brain banks in California and Wisconsin between January 1, 1990, and December 31, 2016. Neither site had preexisting social metrics available for their decedents. Neuropathologic features were obtained from each site for data collected using the standardized Neuropathology Data Set form and from autopsy reports. Data were analyzed from June 7 to October 10, 2019. Exposures:Geocoded decedent addresses linked to neighborhood disadvantage as measured by the Area Deprivation Index calculated for the year of death. Main Outcomes and Measures:Presence of Alzheimer disease neuropathology. The association between neighborhood disadvantage and Alzheimer disease neuropathology was evaluated via logistic regression, adjusting for age, sex, and year of death. Results:The sample consisted of 447 decedents (249 men [56%]; mean [SD] age, 80.3 [9.5] years; median year of death, 2011) spanning 24 years of donation. Fewer decedents (n?=?24 [5.4%]) originated from the top 20% most disadvantaged neighborhood contexts. Increasing neighborhood disadvantage was associated with an 8.1% increase in the odds of Alzheimer disease neuropathology for every decile change on the Area Deprivation Index (adjusted odds ratio, 1.08; 95% CI, 1.07-1.09). As such, living in the most disadvantaged neighborhood decile was associated with a 2.18 increased odds of Alzheimer disease neuropathology (adjusted odds ratio, 2.18; 95% CI, 1.99-2.39). Conclusions and Relevance:The findings of this cross-sectional study suggest that social determinants of health data can be linked to preexisting autopsy samples as a means to study sociobiological mechanisms involved in neuropathology. This novel technique has the potential to be applied to any brain bank within the United States. To our knowledge, this is the first time Alzheimer disease neuropathology has been associated with neighborhood disadvantage.

Dataset Information

Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology.

Objective

Methods

Results

Conclusions

Publications

Neuropsychological changes in asymptomatic persons with Alzheimer disease neuropathology.

Similar Datasets

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