Article

Cholesterol as a risk factor for dementia and cognitive decline: a systematic review of prospective studies with meta-analysis.

Ageing Research Unit, Centre for Mental Health Research, Australian National University, Canberra ACT, Australia.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 3.35). 06/2008; 16(5):343-54. DOI: 10.1097/JGP.0b013e31816b72d4
Source: PubMed

ABSTRACT The relationships between total serum cholesterol (TC) and dementia and between TC and cognitive decline were investigated in a systematic review of 18 prospective studies. Follow-ups ranged from 3 to 29 years, and included a total of 14,331 participants evaluated for Alzheimer disease (AD), 9,458 participants evaluated for Vascular dementia (VaD), 1,893 participants evaluated for cognitive decline, and 4,793 participants evaluated for cognitive impairment. Compatible results were pooled using meta-analysis. Consistent associations between high midlife TC and increased risk of AD, and high midlife TC and increased risk of any dementia were found. There was no evidence supporting an association between late-life TC and AD, or between late-life TC and any dementia. No study reported a significant association between TC (measured in midlife or late-life) and VaD. An association between high midlife TC and cognitive impairment was found but there was only weak evidence for an association between TC and cognitive decline. Two of seven studies reporting data on the interaction between TC and apolipoprotein e4-allele had significant effects. Results suggest the effect of TC on dementia risk occurs in midlife but not late-life, and that there may be different cardiovascular risk factor profiles for AD and VaD. Results from additional studies involving long-term follow-up of midlife samples will allow for clarification of the association between age, TC and risk of specific types of dementia. These data are required to inform recommendations of modulation of cholesterol to reduce or delay dementia risk.

0 Bookmarks
 · 
65 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition. Method: The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies. Results: There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies. Conclusions: Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.
    American Journal of Psychiatry 02/2015; DOI:10.1176/appi.ajp.2014.14070878 · 13.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Co-morbidity and systemic inflammation as drivers of cognitive decline: new experimental models adopting a broader paradigm in dementia research Abstract Dementia prevalence increases with age and Alzheimer's disease (AD) accounts for up to 75% of cases. However, significant variability and overlap exists in the extent of amyloid-β and Tau pathology in AD and non-demented populations and it is clear that other factors must influence progression of cognitive decline, perhaps independent of effects on amyloid pathology. Coupled with the failure of amyloid-clearing strategies to provide benefits for AD patients, it seems necessary to broaden the paradigm in dementia research beyond amyloid deposition and clearance. Evidence has emerged from alternative animal model approaches as well as clinical and population epidemiological studies that co-morbidities contribute significantly to neurodegeneration/cognitive decline and systemic inflammation has been a strong common theme in these approaches. We hypothesise, and discuss in this review, that a disproportionate inflammatory response to infection, injury or chronic peripheral disease is a key determinant of cognitive decline. We propose that detailed study of alternative models, which encompass acute and chronic systemic inflammatory co-morbidities, is an important priority for the field and we examine the cognitive consequences of several of these alternative experimental approaches. Experimental models of severe sepsis in normal animals or moderate acute systemic inflammation in animals with existing neurodegenerative pathology have uncovered roles for inflammatory mediators interleukin-1β, tumour necrosis factor-α, inducible nitric oxide synthase, complement, prostaglandins and NADPH oxidase in inflammation-induced cognitive dysfunction and neuronal death. Moreover, microglia are primed by existing neurodegenerative pathology to produce exaggerated responses to subsequent stimulation with bacterial lipopolysaccharide or other inflammatory stimuli and these insults drive acute dysfunction and negatively affect disease trajectory. Chronic co-morbidities, such as arthritis, atherosclerosis, obesity and diabetes, are risk factors for subsequent dementia and those with high inflammatory status are particularly at risk. Models of chronic co-morbidities, and indeed low grade systemic inflammation in the absence of specific pathology, indicate that interleukin-1β, tumour necrosis factor-α and other inflammatory mediators drive insulin resistance, hypothalamic dysfunction, impaired neurogenesis and cognitive function and impact on functional decline. Detailed study of these pathways will uncover important mechanisms of peripheral inflammation-driven cognitive decline and are already driving clinical initiatives to mitigate AD progression through minimising systemic inflammation.
    Alzheimer's Research and Therapy 03/2015; DOI:10.1186/s13195-015-0117-2 · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimTo investigate perceptions of dementia and dementia risk reduction held by people without dementia.Background Dementia does not only affect individuals with dementia, but also has an impact on family and friends, society and healthcare professionals. Recent research has identified modifiable risk and protective factors for dementia. However, it is unclear what knowledge people without dementia have about these risk factors and their attitudes towards addressing these risk factors to achieve dementia risk reduction are not known.DesignQualitative descriptive study using focus group methodology.MethodA focus group study was conducted in February 2011 with 34 older adults aged between 52-90 years. The long-table approach was used to identify themes and categorize data on dementia knowledge, risk and attitudes.FindingsParticipants correctly identified dementia risk factors as a group. Participants' responses about their perceived likelihood of developing dementia could be classified into three distinctive themes; fear, rational and cynical perceptions. Both fear of developing dementia and the need to improve dementia knowledge were considered major motivators towards adopting healthier lifestyle and health behaviours. Lack of knowledge on risk factors for dementia was identified as a major barrier for behavioural and lifestyle change.Conclusion These findings can be used to develop effective and personalized interventions that increase motivators and reduce barriers by tailoring interventions to individual's dementia risk reduction literacy and motivations to change behaviours. Greater public-health promotion and education about risk and protective factors for dementia are also necessary to increase dementia health literacy and to reduce overall dementia prevalence.
    Journal of Advanced Nursing 02/2015; DOI:10.1111/jan.12641 · 1.69 Impact Factor