Cognitive and Anatomic Contributions of Metabolic Decline in Alzheimer Disease and Cerebrovascular Disease

Abstract

Background: Alzheimer disease and cerebrovascular disease affect elderly persons through alterations in brain structure and metabolism that produce cognitive decline. Understanding how each disease contributes to dementia is essential from both a pathophysiologic and diagnostic perspective. Objective: To elucidate how baseline cognitive function (episodic memory and executive function) and brain anatomy (white matter hyperintensities and hippocampal volume) are associated with baseline (positron emission tomography-1 [PET1]) and longitudinal (PET2) glucose metabolism in 38 subjects older than 55 years ranging from normal cognition, cognitive impairment without dementia, and dementia. Design: Cross-sectional regression analyses across subjects. Setting: Multicenter, university-based study of subcortical vascular dementia. Main Outcome Measures: Regional cerebral glucose metabolism was the primary outcome, with the major hypotheses that memory and hippocampal volume are related to temporoparietal hypometabolism while executive function and white matter hyperintensities correlate with frontal lobe hypometabolism. Results: Low baseline hippocampal volume predicted longitudinal development (PET2) of medial temporal hypometabolism. Lower memory was associated with parietal and cingulate hypometabolism at PET1, which increased at the 2-year-follow-up (PET2). Executive function was associated with frontal and temporoparietal hypometabolism at PET1 but only with frontal hypometabolism at follow-up. White matter hyperintensities predicted hypometabolism over time in the frontoparietal regions, predicting a rate of metabolic change (PET1−PET2/time). Conclusions: Low baseline episodic memory and hippocampal volume predict the metabolic alterations associated with Alzheimer disease, whereas elevated baseline white matter hyperintensities predict a different pattern of metabolic decline that is plausibly associated with cerebrovascular disease.

Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

“…Our results are in line with previous studies which revealed negative relationships between measures of WML volume and global [Kochunov et al, 2009] and regional (mostly frontal) glucose metabolism [DeCarli et al, 1995; Kuczynski et al, 2008; Reed et al, 2004; Sultzer et al, 2002; Tullberg et al, 2004]. With regard to the PIB/WML relationship an interesting picture emerges.…”

Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

“…Our results are in line with previous studies which revealed negative relationships between measures of WML volume and global [Kochunov et al, 2009] and regional (mostly frontal) glucose metabolism [DeCarli et al, 1995; Kuczynski et al, 2008; Reed et al, 2004; Sultzer et al, 2002; Tullberg et al, 2004]. With regard to the PIB/WML relationship an interesting picture emerges.…”

Neuropathological Associates of Multiple Cognitive Functions in Two Community-Based Cohorts of Older Adults

“…Using Pratt’s measure of relative importance, cortical NFTs were approximately 3 times more important than medial temporal NFTs for predicting episodic memory. Such findings correspond to a growing body of literature suggesting that various aspects of memory are dependent on a distributed set of brain regions including prefrontal regions (Dickerson et al, 2009; Kirchhoff, Wagner, Maril, & Stern, 2002) and posterior parietal regions (Kuczynski et al, 2008; Staresina & Davachi, 2006; Walhovd et al, 2010). Although there is some literature reporting a specific relationship between medial temporal tangle pathology and episodic memory (Mitchell et al, 2002), we are unaware of any previous studies that have compared the association of NFT across different regions with specific cognitive functions.…”

White matter integrity and cortical metabolic associations in aging and dementia

“…Our FDG-PET regression analysis with MMSE revealed a predominant left hemispheric hypometabolism, which would consequently affect our FA associations. Left hemispheric dominance, especially within the temporoparietal regions, has been observed in many metabolic studies and is obviously dependent on the composition of the cohort and, when relevant, the covariate used in the analysis [15, 40, 41]. Our metabolic correlations with MMSE also support our restricted FA associations between the left IFWM and temporal regions.…”

Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

“…Our results are in line with previous studies which revealed negative relationships between measures of WML volume and global [Kochunov et al, 2009] and regional (mostly frontal) glucose metabolism [DeCarli et al, 1995; Kuczynski et al, 2008; Reed et al, 2004; Sultzer et al, 2002; Tullberg et al, 2004]. With regard to the PIB/WML relationship an interesting picture emerges.…”

Neuropathological Associates of Multiple Cognitive Functions in Two Community-Based Cohorts of Older Adults

“…Using Pratt’s measure of relative importance, cortical NFTs were approximately 3 times more important than medial temporal NFTs for predicting episodic memory. Such findings correspond to a growing body of literature suggesting that various aspects of memory are dependent on a distributed set of brain regions including prefrontal regions (Dickerson et al, 2009; Kirchhoff, Wagner, Maril, & Stern, 2002) and posterior parietal regions (Kuczynski et al, 2008; Staresina & Davachi, 2006; Walhovd et al, 2010). Although there is some literature reporting a specific relationship between medial temporal tangle pathology and episodic memory (Mitchell et al, 2002), we are unaware of any previous studies that have compared the association of NFT across different regions with specific cognitive functions.…”

White matter integrity and cortical metabolic associations in aging and dementia

“…Our FDG-PET regression analysis with MMSE revealed a predominant left hemispheric hypometabolism, which would consequently affect our FA associations. Left hemispheric dominance, especially within the temporoparietal regions, has been observed in many metabolic studies and is obviously dependent on the composition of the cohort and, when relevant, the covariate used in the analysis [15, 40, 41]. Our metabolic correlations with MMSE also support our restricted FA associations between the left IFWM and temporal regions.…”

Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter

“…Our results are in line with previous studies which revealed negative relationships between measures of WML volume and global [Kochunov et al, 2009] and regional (mostly frontal) glucose metabolism [DeCarli et al, 1995; Kuczynski et al, 2008; Reed et al, 2004; Sultzer et al, 2002; Tullberg et al, 2004]. With regard to the PIB/WML relationship an interesting picture emerges.…”

Neuropathological Associates of Multiple Cognitive Functions in Two Community-Based Cohorts of Older Adults

“…Using Pratt’s measure of relative importance, cortical NFTs were approximately 3 times more important than medial temporal NFTs for predicting episodic memory. Such findings correspond to a growing body of literature suggesting that various aspects of memory are dependent on a distributed set of brain regions including prefrontal regions (Dickerson et al, 2009; Kirchhoff, Wagner, Maril, & Stern, 2002) and posterior parietal regions (Kuczynski et al, 2008; Staresina & Davachi, 2006; Walhovd et al, 2010). Although there is some literature reporting a specific relationship between medial temporal tangle pathology and episodic memory (Mitchell et al, 2002), we are unaware of any previous studies that have compared the association of NFT across different regions with specific cognitive functions.…”

White matter integrity and cortical metabolic associations in aging and dementia

“…Our FDG-PET regression analysis with MMSE revealed a predominant left hemispheric hypometabolism, which would consequently affect our FA associations. Left hemispheric dominance, especially within the temporoparietal regions, has been observed in many metabolic studies and is obviously dependent on the composition of the cohort and, when relevant, the covariate used in the analysis [15, 40, 41]. Our metabolic correlations with MMSE also support our restricted FA associations between the left IFWM and temporal regions.…”