Interreg-IPA Cross-border Cooperation Programme Romania ...neuro-vascular-dementia.eu/images/editoriale/... · – between 3 and 45%, – limited to community-dwelling MCI patients

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

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%

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

• Occurrence of anxiety might be a preventable risk factor for dementia when still young

• Possibly accelerates a destructive chain reaction at an advanced age

Introduction

• The prevalence rate of anxiety in MCI– between 3 and 45%, – limited to community-dwelling MCI patients

between 2 and 4%

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

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.

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.

• 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

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

• 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.

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

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

• 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

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

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

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

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

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.

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

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

Conclusion

• Preventive potential of treating anxiety• CBT?• Trait anxiety – modifiable risk factor?

Thank you