Lipid metabolism in cognitive decline and dementia

Panza, Francesco; D’Introno, Alessia; Colacicco, Anna M.; Capurso, Cristiano; Pichichero, Gianfranco; Capurso, Sabrina A.; Capurso, Antonio; Solfrizzi, Vincenzo

doi:10.1016/j.brainresrev.2005.11.007

Cited by 159 publications

(126 citation statements)

References 171 publications

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“…Indeed, these different fi ndings may be due to the fact that total cholesterol decreases with age (Postglione et al 1989) and insuffi cient nutrition, and that, several years before dementia, blood pressure and BMI begin to decline, possibly as a result of the ongoing AD pathology, suggesting that the same may be true for TC (Panza et al 2006). Decreased cholesterol might be an effect rather than a cause of dementia.…”

Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 96%

“…Several epidemiological studies have assessed the link between cholesterol levels and dementia, especially AD (Panza et al 2006). Cross-sectional studies provided very confl icting results.…”

Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 99%

“…Mechanisms which could explain the effects of ApoE on the brain of AD subjects are still unclear. They include isoform specifi c toxicity, ApoE ε4-mediated amyloid aggregation, ApoE ε4-mediated tau hyperphosphorylation, and isoform-driven ApoE concentration changes (Panza et al 2006). ApoE could also modulate the distribution and metabolism of cholesterol in neuronal membranes in an isoform-dependent manner, which may be relevant to Apo E-related pathogenic effects and the development of AD (Yanasigawa 2002).…”

Section: Apolipoprotein E Genotype and Cognitive Declinementioning

confidence: 99%

“…The pathophysiological mechanisms linking cholesterol metabolism to AD are still unknown (Wolozin 2004;Shobab et al 2005;Panza et al 2006). Cholesterol infl uences the activity of the enzymes involved in the metabolism of the amyloid precursor protein and in the production of Aβ.…”

Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 99%

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Vascular risk factors, cognitve decline, and dementia

Duron

Hanon²

2008

VHRM

245

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Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer's disease. Some longitudinal studies, have found signifi cant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fi brillation, smoking, and dementia have given more confl icting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.

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Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 96%

Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 99%

Section: Apolipoprotein E Genotype and Cognitive Declinementioning

confidence: 99%

Section: Cholesterol Statins and Cognitive Declinementioning

confidence: 99%

See 2 more Smart Citations

Vascular risk factors, cognitve decline, and dementia

Duron

Hanon²

2008

VHRM

245

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“…Although earlier observational studies on the relationship between HDL-C levels and cognitive function produced conflicting results (see 12,13 for review), low plasma concentrations of HDL-C have been repeatedly reported in association with dementia. As the majority of earlier studies were cross-sectional, the present study is clearly distinct as a result of the evaluation of both cross-sectional and prospective associations.…”

Section: See Accompanying Article On Page 1556mentioning

confidence: 99%

HDL: Close to Our Memories?

Kontush

Chapman

2008

ATVB

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T he last decade has witnessed an explosion in studies of the role of lipoproteins in brain function. Neurons require a continuous supply of lipids for membrane synthesis and acetylcholine production. Indeed, the brain is a site of intense lipid turnover-even though the central nervous system (CNS) accounts for only 2.1% of body weight, it contains 23% of total body cholesterol. 1 Lipid metabolism in the brain is tightly controlled locally, as plasma lipoproteins are shielded from the brain by the blood-brain barrier. Although neuronal cells are capable of de novo synthesis of a wide spectrum of molecular species of lipids, they rely heavily on exogenous sources and readily bind and internalize lipoproteins of the extracellular fluid. 2 Equally, neurons need to dispose of excess lipids; lipoprotein-mediated lipid transport is therefore bidirectional and includes cellular efflux of cholesterol. 3 See accompanying article on page 1556Human cerebrospinal fluid (CSF) primarily contains spherical lipoproteins of approximately 10 to 12 nm in diameter with hydrated density in the range 1.063 to 1.25 g/mL, thereby resembling HDL in human plasma. 3,4 Lipid concentrations in CSF are however much lower (eg, 300-to 400-fold for total cholesterol and phospholipids) as compared to the plasma compartment. 4 Apolipoproteins (apo) E and A-I are the major apolipoproteins in human CSF (typical concentration range: 0.1 to 0.4 mg/dL 3,4 ), with apoA-II, A-IV, J, D, C-II, C-III, C-IV, and H equally present. 3,4 Importantly, CSF lipoproteins carry amyloid-␤ (A␤), a 39-to 43-aa peptide produced in neuronal cells, which is the major component of senile amyloid plaques. 5 The metabolism of CSF lipoproteins remains poorly characterized but seems to be distinct from that of plasma lipoproteins. ApoE-rich HDL are synthesized locally in CNS and secreted by astrocytes as discoidal complexes enriched in free cholesterol. 6 High apoE content targets these lipoproteins to cellular apoE receptors, particularly LDL receptor-related protein, which is abundantly expressed on the surface of neurons. 2 By contrast, apoA-I-rich CSF lipoproteins are most probably derived from plasma HDL that enter the CNS by crossing the blood-brain barrier, 7 as apoA-I is not synthesized in the CNS. 2 Similar to plasma HDL, CSF lipoproteins can be remodeled by lecithin-cholesterol acyltransferase and phospholipid transfer protein; by contrast, cholesteryl ester transfer protein (CETP) is absent from CSF. 3 These data clearly demonstrate that brain HDL constitute a key element of cholesterol homeostasis in the CNS.Over the past decade, abnormalities in brain lipid metabolism are increasingly recognized to be intimately related to the pathogenesis of such major neurodegenerative disorders as Alzheimer disease (AD) and vascular dementia (VD). With respective frequencies of 70% and 15% of all dementias, AD and VD are the most common forms of dementia which are typically preceded by less dramatic cognitive decline, including decline in memory. 8 Both AD and atherosclerosis ...

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