interreg-ipa cross-border cooperation programme romania...
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Interreg-IPA Cross-border Cooperation Programme Romania-Serbia
Vuk VukovićFebruary 2019
Anxiety as a risk factor of Alzheimer’s disease and vascular dementia
Employment promotion and basic services strengthening for an inclusive growth
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Introduction
• Alzheimer’s disease has an expected doubling of patients every 20 years
• Vascular dementia second most common dementia
• Prevalence– AD 4.2% (over 65)– VD 1%
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Introduction
• Depression and anxiety are among the most common neuropsychiatric symptoms presenting in MCI
• Depressive symptoms predicts conversion from MCI to dementia as well as incident dementia in the general population
• Effect of anxiety is less clear as studies are scarce and vary in methodology
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• Occurrence of anxiety might be a preventable risk factor for dementia when still young
• Possibly accelerates a destructive chain reaction at an advanced age
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Introduction
• The prevalence rate of anxiety in MCI– between 3 and 45%, – limited to community-dwelling MCI patients
between 2 and 4%
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Introduction
• One meta-analysis - anxiety associated with higher risk for incident cognitive impairment, possibly for incident dementia in community samples.
• The association of anxiety and conversion to dementia greater in 80 years and older
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Pathogenesis
• Various anxiety-associated factors like inflammation and oxidative stress are linked to the pathogenesis of both types of dementia.
• Anxiety is characterised by enduring anticipation and permanent neurotoxic distress.
• Especially in old age, neurons are susceptible to the damaging effects of glucocorticoids.
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Anxiety and Alzheimer’s disease
• Two studies association between trait anxiety and AD
• Results not adjusted for depression(possible bias)
• Findings were independent from gender
• Plausible that trait anxiety promotes permanent brain-damaging stress.
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• Personality traits are not correlated to neuropathogenic lesions, suggesting that reduced cognitive reserve might be a crucial pathomechanism.
• damaging pathway of anxiety and stress is likely to be independent from sex hormones.
• anxiety is not a sufficient explanation why Alzheimer’s disease occurs more frequently in women
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Anxiety and Alzheimer’s disease
• Individuals with both anxious and depressive symptoms at higher risk ofAlzheimer’s disease
• Plausible according to cumulative stress hypothesis
• No significant relationship to ICD or DSM diagnoses of anxiety
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• According to the stress hypothesis, trait anxiety might provoke chronic distress and allostatic load throughout life, whereas anxiety disorders differ in typical age at onset.
• the effect of specific anxiety disorders on cognitive health might be different because ofprognosis.
• In this sys- tematic review, only one study provided information about subtypes, but no association with regard to Alzheimer’s disease was found for generalised anxiety disorder, specific phobia and agoraphobia.
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Anxiety and Alzheimer’s disease
• Catalytic effect of anxiety• Anhedonia and withdrawal lead
inactivity and reduced stimulation• Whereas affirmation of life and lifestyle
might be less impaired in people with anxiety disorders.
• Melancholia but not comorbid anxiety in patients with depression predictive factor with regard to future dementia
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Anxiety and vascular dementia
• Few studies• Depression but not anxiety associated to
future VD• VD often accompanied by anxiety
disorders.• Connection could be driven by
– comorbid cardiovascular disease and risk factors,
– depression, – substance misuse and – health-damaging behaviour in general
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• Anxiety - vascular damage - via hypercoagulability, atherosclerosis and hypertension
• Studies controlled cardiovascular risk factors and cardiovascular diseases
• Psychological distress is a shared feature within the course of AD and VD
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Stress and dementia
• Many epidemiological studies on relationship of stress and dementia
• Wilson et al. (2003) – 806 elderly – follow-up of 4.9 years – high in stress proneness (90th percentile)
twice the risk
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Stress and dementia
• Tsolaki et al., 2003– 149 Orthodox monks and nuns from Greek
and Cyprus monasteries – less stress might not prevent the
appearance of dementia, delays the onset of symptoms.
• Indicating the possible relationship between long-term life stress and dementia onset
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Chronic stres
• Chronic stress enhances the sensitivity to inflammatory processes of the brain areas affected in AD
• Chronic stress accelerates the rate of aging, which could be related to the onset of AD
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Chronic stress
• The HPA axis seems to be the first mechanism by which chronic stress is able to produce its effect.
• Increase in GC levels would appear to be the ultimate consequence of stress
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Chronic stress
• Chronic stress/GCs enhances the main processes that appear to be involved in aging, such as the – impairment of mitochondrial function, the – decrease in energetic metabolism and the – increase in oxidative damage, – enhancing cell vulnerability, especially in those
brain areas with a high GCR concentration.
• These processes seem to be involved in the increase and accumulation of Aβ, the main feature of AD.
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stress/dementia animal models
• Different animal models of AD report that stress and high concentration of GCs produced an increase of Aβ toxicity and the acceleration of AD features
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Conclusion
• Anxiety likely to damage the brain – directly by permanent stress and – indirectly by avoidant behaviour, inactive
lifestyle and loss of cognitive reserve and resiliency.
• The temporal or functional relation between anxiety and dementia needs more careful investigation
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Conclusion
• Preventive potential of treating anxiety• CBT?• Trait anxiety – modifiable risk factor?
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Thank you