Background: The relationship between cerebrovascular disease (CVD) risk factors and cognitive imp... more Background: The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively (using MRI T2 volumetric analysis of white matter hyperintensity (WMH) volumes), would identify specific CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type (MCI-CVD), that represent the core features of vascular cognitive impairment in our Kentucky “stroke-belt” population, at risk for cognitive decline and the future development of dementia. Methods: A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) and mild cognitive impairment (MCI; n=62) was performed. Quantitative total WMH volumes were examined in relation to potentially causative CVD risk factors and resultant test scores across cognitive domains using linear regression models adjusted for age, gender, and education. Results: Among CVD risk factors analyzed, age (p< 0.001), education (p= 0.003), hypertension (p= 0.012), and hyperlipidemia (p= 0.008) demonstrated the strongest associations with WMH volumes. Conversely, CVD risk factors such as diabetes, smoking, history of heart attacks, atrial fibrillation, and history of stroke that have shown associations with CVD pathology on imaging in other studies were not statistically associated with increased WMH in this cohort. Unexpectedly, Framingham risk scores (FRS) and modified (short version) Hachinski Ischemic Scale (HIS) measures were not statistically associated with quantitative WMH volumes in this study. WMH volumes were associated with decrease performance on the Trial Making Test type A & B and long delayed free recall on the California Verbal Learning Test. Conclusion: Our findings suggest similarities and yet differences in comparison to other studies, regarding the impact of CVD risks and associations with cognitive performance with the development of CVD pathology measured by WMH on MRI. Hypertension and hyperlipidemia appear to represent common shared risks across geographically disparate groups. Our findings, like others, suggest CVD pathology impact processing speed and executive function and provide further evidence for CVD effects on short-term memory in those at risk for cognitive decline and the future development of dementia in our Kentucky “stroke-belt” population.
Journal of neuropathology and experimental neurology, Jan 21, 2016
The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative di... more The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD "mimic," which has been termed "hippocampal sclerosis of aging" or "hippocampal sclerosis dementia." This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pa...
Background: The relationship between cerebrovascular disease (CVD) risk factors and cognitive imp... more Background: The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively (using MRI T2 volumetric analysis of white matter hyperintensity (WMH) volumes), would identify specific CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type (MCI-CVD), that represent the core features of vascular cognitive impairment in our Kentucky “stroke-belt” population, at risk for cognitive decline and the future development of dementia. Methods: A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) and mild cognitive impairment (MCI; n=62) was performed. Quantitative total WMH volumes were examined in relation to potentially causative CVD risk factors and resultant test scores across cognitive domains using linear regression models adjusted for age, gender, and education. Results: Among CVD risk factors analyzed, age (p< 0.001), education (p= 0.003), hypertension (p= 0.012), and hyperlipidemia (p= 0.008) demonstrated the strongest associations with WMH volumes. Conversely, CVD risk factors such as diabetes, smoking, history of heart attacks, atrial fibrillation, and history of stroke that have shown associations with CVD pathology on imaging in other studies were not statistically associated with increased WMH in this cohort. Unexpectedly, Framingham risk scores (FRS) and modified (short version) Hachinski Ischemic Scale (HIS) measures were not statistically associated with quantitative WMH volumes in this study. WMH volumes were associated with decrease performance on the Trial Making Test type A & B and long delayed free recall on the California Verbal Learning Test. Conclusion: Our findings suggest similarities and yet differences in comparison to other studies, regarding the impact of CVD risks and associations with cognitive performance with the development of CVD pathology measured by WMH on MRI. Hypertension and hyperlipidemia appear to represent common shared risks across geographically disparate groups. Our findings, like others, suggest CVD pathology impact processing speed and executive function and provide further evidence for CVD effects on short-term memory in those at risk for cognitive decline and the future development of dementia in our Kentucky “stroke-belt” population.
Journal of neuropathology and experimental neurology, Jan 21, 2016
The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative di... more The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD "mimic," which has been termed "hippocampal sclerosis of aging" or "hippocampal sclerosis dementia." This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pa...
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Methods: A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) and mild cognitive impairment (MCI; n=62) was performed. Quantitative total WMH volumes were examined in relation to potentially causative CVD risk factors and resultant test scores across cognitive domains using linear regression models adjusted for age, gender, and education.
Results: Among CVD risk factors analyzed, age (p< 0.001), education (p= 0.003), hypertension (p= 0.012), and hyperlipidemia (p= 0.008) demonstrated the strongest associations with WMH volumes. Conversely, CVD risk factors such as diabetes, smoking, history of heart attacks, atrial fibrillation, and history of stroke that have shown associations with CVD pathology on imaging in other studies were not statistically associated with increased WMH in this cohort. Unexpectedly, Framingham risk scores (FRS) and modified (short version) Hachinski Ischemic Scale (HIS) measures were not statistically associated with quantitative WMH volumes in this study. WMH volumes were associated with decrease performance on the Trial Making Test type A & B and long delayed free recall on the California Verbal Learning Test.
Conclusion: Our findings suggest similarities and yet differences in comparison to other studies, regarding the impact of CVD risks and associations with cognitive performance with the development of CVD pathology measured by WMH on MRI. Hypertension and hyperlipidemia appear to represent common shared risks across geographically disparate groups. Our findings, like others, suggest CVD pathology impact processing speed and executive function and provide further evidence for CVD effects on short-term memory in those at risk for cognitive decline and the future development of dementia in our Kentucky “stroke-belt” population.
Methods: A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) and mild cognitive impairment (MCI; n=62) was performed. Quantitative total WMH volumes were examined in relation to potentially causative CVD risk factors and resultant test scores across cognitive domains using linear regression models adjusted for age, gender, and education.
Results: Among CVD risk factors analyzed, age (p< 0.001), education (p= 0.003), hypertension (p= 0.012), and hyperlipidemia (p= 0.008) demonstrated the strongest associations with WMH volumes. Conversely, CVD risk factors such as diabetes, smoking, history of heart attacks, atrial fibrillation, and history of stroke that have shown associations with CVD pathology on imaging in other studies were not statistically associated with increased WMH in this cohort. Unexpectedly, Framingham risk scores (FRS) and modified (short version) Hachinski Ischemic Scale (HIS) measures were not statistically associated with quantitative WMH volumes in this study. WMH volumes were associated with decrease performance on the Trial Making Test type A & B and long delayed free recall on the California Verbal Learning Test.
Conclusion: Our findings suggest similarities and yet differences in comparison to other studies, regarding the impact of CVD risks and associations with cognitive performance with the development of CVD pathology measured by WMH on MRI. Hypertension and hyperlipidemia appear to represent common shared risks across geographically disparate groups. Our findings, like others, suggest CVD pathology impact processing speed and executive function and provide further evidence for CVD effects on short-term memory in those at risk for cognitive decline and the future development of dementia in our Kentucky “stroke-belt” population.