Memory Deficit in Middle Age Linked to Low HDL
By Charles Bankhead
VILLEJUIF, France, 1 july 2008-- Middle-age patients with an HDL of less than 40 mg/dL had significantly poorer short-term verbal memory, an examination of links between lipid levels and cognitive function revealed.
Moreover, a decline in memory over a five-year period paralleled a decrease in HDL, Archana Singh-Manoux, Ph.D., of the French National Institute for Health and Medical Research, and colleagues reported in Arteriosclerosis, Thrombosis, and Vascular Biology.
"The 'life-long' view of dementia stresses the importance of risk factors in midlife," the authors said. "Our findings on individuals ages 55 and 61 at the two phases of data collection suggest that low levels of HDL-C may be an important risk factor."
A commonality in risk factors for cardiovascular disease and dementia has helped blur the distinction between vascular dementia and Alzheimer's disease, they said.
And, although high cholesterol is a proven risk factor for cardiovascular disease, the association with cognition has been complicated by inconsistent findings from various studies. Moreover, studies of lipid-lowering therapies -- most of which dealt with LDL or total cholesterol -- have yielded mixed results with respect to cognitive function, the researchers continued.
Associations with HDL have remained largely unexplored. To address that limitation, the researchers examined data from Whitehall II, a long-term cohort study involving 10,308 British civil servants.
The current analysis comprised 3,673 men and women who participated in two Whitehall II data-collection periods: 1995 to 1997 and 2002 to 2004. Lipid profiles were evaluated during both periods, and short-term verbal memory was assessed by means of a 20-word list.
Using lipid categories from the 2001 report of the National Cholesterol Education Program, the investigators examined associations between lipids and memory deficit, defined as recall of four or fewer words or a decrease of two or more words between the two data-collection periods.
As compared with high HDL levels (60 mg/dL or greater), low HDL (40 mg/dL or less) was associated with a nonsignificant memory deficit at the first data-collection period (OR 1.27, 95% CI 0.91 to 1.77), when participants had a median age of 55.
The difference increased during the five-year interval between data collection and became statistically significant during the second period (OR 1.53, 95% CI 1.04 to 2.25), when participants were a median 61 years of age.
Moreover, a decline in HDL between the two periods had a significant association with a decline in memory (OR 1.61, 95% CI 1.19 to 2.16).
The differences emerged after adjustment for education, occupational position, coronary heart disease, stroke, hypertension, medication use, diabetes, smoking, and alcohol consumption. The investigators also found no evidence of interaction with APOE e4 genotype, a risk factor for Alzheimer's disease.
The study showed no association between memory deficit or decline and either total cholesterol or triglycerides.
The authors cited several possible mechanisms that could account for associations between HDL and cognitive function:
Regulation of β-amyloid production and deposition in the brain
Modification of the risk for cerebral atherosclerosis, stroke, and subclinical vascular disease
Neurodegenerative processes related to anti-inflammatory or antioxidant properties
The authors also noted that lipid levels can fluctuate over the course of the evolution and progression of dementia, making the time-point of measurement a critical issue.
In an accompanying editorial, Anatol Kontush, Ph.D., and M. John Chapman, Ph.D., D.Sc., of Pierre and Marie Curie University in Paris, said "low plasma concentrations of HDL-C have been repeatedly reported in association with dementia. ... Moreover, elevated HDL-C levels ... are also associated with longevity, improved cognition, and dementia-free survival."
With respect to potential underlying mechanisms cited by the authors, the editorialists said, "In all of these scenarios, it remains unclear as to how low levels of HDL-C measured in plasma can be translated into defective functionality of HDL in the brain."
In conclusion, Drs. Kontush and Chapman said, "HDL-C remains a potentially promising but still remote target in the prevention of dementia and memory loss. Nonetheless, these studies demand that we focus more effort on research at the interface between HDL and brain function."
The Whitehall II study was supported by grants from the British Medical Research Council, the British Heart foundation, the British Health and Safety Executive, the British Department of Health, the National Heart, Lung, and Blood Institute, the Agency for Health Care Policy and Research, and the John D. and Catherine T. MacArthur Foundation.
The authors said they had no disclosures. The editorialists made no disclosures.
Primary source: Arteriosclerosis, Thrombosis, and Vascular BiologySource reference:Singh-Manous, A et al "Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife. The Whitehall II Study" Arterioscler Thromb Vasc Biol 2008; 28: DOI:10.1161/ATVBAHA.108.163998. Additional source: Arteriosclerosis, Thrombosis, and Vascular BiologySource reference: Kontush A, Chapman MJ "HDL: Close to our memories?" Arterioscler Thromb Vasc Biol 2008; 28: epub.
By Charles Bankhead
VILLEJUIF, France, 1 july 2008-- Middle-age patients with an HDL of less than 40 mg/dL had significantly poorer short-term verbal memory, an examination of links between lipid levels and cognitive function revealed.
Moreover, a decline in memory over a five-year period paralleled a decrease in HDL, Archana Singh-Manoux, Ph.D., of the French National Institute for Health and Medical Research, and colleagues reported in Arteriosclerosis, Thrombosis, and Vascular Biology.
"The 'life-long' view of dementia stresses the importance of risk factors in midlife," the authors said. "Our findings on individuals ages 55 and 61 at the two phases of data collection suggest that low levels of HDL-C may be an important risk factor."
A commonality in risk factors for cardiovascular disease and dementia has helped blur the distinction between vascular dementia and Alzheimer's disease, they said.
And, although high cholesterol is a proven risk factor for cardiovascular disease, the association with cognition has been complicated by inconsistent findings from various studies. Moreover, studies of lipid-lowering therapies -- most of which dealt with LDL or total cholesterol -- have yielded mixed results with respect to cognitive function, the researchers continued.
Associations with HDL have remained largely unexplored. To address that limitation, the researchers examined data from Whitehall II, a long-term cohort study involving 10,308 British civil servants.
The current analysis comprised 3,673 men and women who participated in two Whitehall II data-collection periods: 1995 to 1997 and 2002 to 2004. Lipid profiles were evaluated during both periods, and short-term verbal memory was assessed by means of a 20-word list.
Using lipid categories from the 2001 report of the National Cholesterol Education Program, the investigators examined associations between lipids and memory deficit, defined as recall of four or fewer words or a decrease of two or more words between the two data-collection periods.
As compared with high HDL levels (60 mg/dL or greater), low HDL (40 mg/dL or less) was associated with a nonsignificant memory deficit at the first data-collection period (OR 1.27, 95% CI 0.91 to 1.77), when participants had a median age of 55.
The difference increased during the five-year interval between data collection and became statistically significant during the second period (OR 1.53, 95% CI 1.04 to 2.25), when participants were a median 61 years of age.
Moreover, a decline in HDL between the two periods had a significant association with a decline in memory (OR 1.61, 95% CI 1.19 to 2.16).
The differences emerged after adjustment for education, occupational position, coronary heart disease, stroke, hypertension, medication use, diabetes, smoking, and alcohol consumption. The investigators also found no evidence of interaction with APOE e4 genotype, a risk factor for Alzheimer's disease.
The study showed no association between memory deficit or decline and either total cholesterol or triglycerides.
The authors cited several possible mechanisms that could account for associations between HDL and cognitive function:
Regulation of β-amyloid production and deposition in the brain
Modification of the risk for cerebral atherosclerosis, stroke, and subclinical vascular disease
Neurodegenerative processes related to anti-inflammatory or antioxidant properties
The authors also noted that lipid levels can fluctuate over the course of the evolution and progression of dementia, making the time-point of measurement a critical issue.
In an accompanying editorial, Anatol Kontush, Ph.D., and M. John Chapman, Ph.D., D.Sc., of Pierre and Marie Curie University in Paris, said "low plasma concentrations of HDL-C have been repeatedly reported in association with dementia. ... Moreover, elevated HDL-C levels ... are also associated with longevity, improved cognition, and dementia-free survival."
With respect to potential underlying mechanisms cited by the authors, the editorialists said, "In all of these scenarios, it remains unclear as to how low levels of HDL-C measured in plasma can be translated into defective functionality of HDL in the brain."
In conclusion, Drs. Kontush and Chapman said, "HDL-C remains a potentially promising but still remote target in the prevention of dementia and memory loss. Nonetheless, these studies demand that we focus more effort on research at the interface between HDL and brain function."
The Whitehall II study was supported by grants from the British Medical Research Council, the British Heart foundation, the British Health and Safety Executive, the British Department of Health, the National Heart, Lung, and Blood Institute, the Agency for Health Care Policy and Research, and the John D. and Catherine T. MacArthur Foundation.
The authors said they had no disclosures. The editorialists made no disclosures.
Primary source: Arteriosclerosis, Thrombosis, and Vascular BiologySource reference:Singh-Manous, A et al "Low HDL cholesterol is a risk factor for deficit and decline in memory in midlife. The Whitehall II Study" Arterioscler Thromb Vasc Biol 2008; 28: DOI:10.1161/ATVBAHA.108.163998. Additional source: Arteriosclerosis, Thrombosis, and Vascular BiologySource reference: Kontush A, Chapman MJ "HDL: Close to our memories?" Arterioscler Thromb Vasc Biol 2008; 28: epub.
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