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Vascular risk factors contribute to idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective

The objective was to determine the complete modern vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative INPH-patients and population-based controls, in order to confirm the impact of vascular disease on INPH pathophysiology.

 

Methods

All shunted INPH-patients in Sweden 2008-2010 were compared to age- and gender-matched population-based controls. Inclusion criteria: 60-85 years and mini mental state estimation ³23. The ten most important modern VRFs as well as cerebrovascular and peripheral vascular disease were prospectively assessed through blood samples, by-protocol clinical examinations and standardized questionnaires. Investigated VRFs: hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking, diet, alcohol intake, cardiac disease and, physical activity.

 

Results

After exclusion, 176 INPH-patients and 368 controls participated. Using multivariable logistic regression, hyperlipidemia (OR: 2.380, 95%CI: 1.434-3.950), diabetes (OR: 2.169, 95%CI: 1.195-3.938), obesity (OR: 5.428, 95%CI: 2.502-11.772) and, psychosocial factors (OR: 5.343, 95%CI: 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, cerebrovascular and peripheral vascular disease were overrepresented in INPH, although not independently. The protective factors: moderate alcohol intake and physical activity were overrepresented among the controls. The population attributable risk percentage was 24%.

 

Conclusions

Our findings confirm that INPH-patients have a more dangerous VRF-profile and lack the protective factors present in the population. Almost one quarter of INPH could be explained by VRF, suggesting that INPH possibly may be a subgroup of vascular dementia. Targeted interventions against modifiable VRF are likely to have beneficial effects in INPH.

Keyword [en]
normal pressure hydrocephalus, vascular risk factors, vascular disease
National Category
Medical and Health Sciences
Research subject
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-120173OAI: oai:DiVA.org:umu-120173DiVA: diva2:927030
Available from: 2016-05-10 Created: 2016-05-10 Last updated: 2016-05-11
In thesis
1. Comorbidity and vascular risk factors  associated with idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Open this publication in new window or tab >>Comorbidity and vascular risk factors  associated with idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a cerebrospinal fluid shunt. It has been suggested that INPH has similar pathophysiological mechanisms as cerebrovascular disease, but the vascular risk factor (VRF) profile of INPH patients has not been assessed using a modern epidemiological approach. The cognitive symptoms of INPH resemble the symptoms of depression, but the prevalence of depression among INPH patients is unknown. In addition, few studies investigate the impact of shunting on the quality of life (QoL), and no study has investigated the impact of comorbidity on QoL in INPH patients.

The objective of this dissertation was to present the VRF profile of INPH and to investigate the hypothesis that INPH may be a subgroup of vascular dementia. Additional objectives were to assess the prevalence of depression in INPH patients and to investigate the impact of shunting and comorbidities on QoL in INPH.

In the first cohort, the prevalence of possible INPH was assessed through clinical and radiological examinations in patients with a transient ischemic attack (TIA), consecutively admitted to the same hospital during 2006-2008. In the second cohort, VRFs, vascular disease and QoL were analysed in INPH patients consecutively shunted 2008-2010 in five out of six neurosurgical centres in Sweden. Patients remaining after inclusion (n=176, within the age-span 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n=368, same inclusion criteria as for the INPH patients). Assessed VRFs were: hypertension, diabetes, obesity, hyperlipidemia, psychosocial factors (stress and depression), smoking, alcohol intake, physical activity and, dietary pattern. Cardiovascular, cerebrovascular and peripheral vascular disease as well as QoL were also assessed. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG and, blood samples.

In the first cohort, 4% of the TIA patients had clinically and radiologically verified INPH. In the second cohort, VRFs were overrepresented among the INPH patients compared with the controls. The VRFs independently associated with INPH were: hyperlipidemia (Odds ratio (OR): 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), obesity (OR: 5.4, 95%CI: 2.5-11.8) and, psychosocial factors (OR: 5.3, 95%CI: 3.2-8.9). When adding the VRFs that were overrepresented in INPH, although not independently (physical inactivity and hypertension), these six VRFs accounted for 24% of the INPH cases in the elderly population (population attributable risk %: 24). Depression was overrepresented in shunted INPH patients compared to the controls (46% vs. 13%, p<0.001) and the main predictor for low QoL was a coexisting depression (p<0.001).

In conclusion, the results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH and indicate that INPH may be subgroup of vascular dementia. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for quality of life should be included in the work-up of INPH patients. The effect of targeted interventions against modifiable VRFs and anti-depressant treatment in INPH patients should be evaluated. 

Abstract [sv]

Idiopatisk normaltryckshydrocefalus (INPH, från engelskans ”idiopathic normal pressure hydrocephalus”) är en neurokirurgiskt behandlingsbar demens. Behandlingen är att operera in en shunt som dränerar cerebrospinalvätska från ventriklarna. Det har föreslagits att INPH skulle kunna orsakas av liknande patofysiologiska mekanismer som vid cerebrovaskulär sjukdom, men den vaskulära riskfaktorprofilen hos INPH-patienter har aldrig undersökts i en modern epidemiologisk studie. De kognitiva symtomen vid INPH påminner om symtomen vid depression, men prevalensen av depression hos INPH-patienter är okänd. Få studier undersöker hur shuntning påverkar livskvalitet och ingen studie har undersökt hur komorbiditet påverkar livskvaliteten vid INPH.

Syftet med den här avhandlingen var att undersöka den vaskulära riskfaktorprofilen hos INPH-patienter samt att utforska hypotesen att INPH skulle kunna vara en undergrupp till vaskulär demens. Ytterligare ett syfte med avhandlingen var att undersöka hur många INPH-patienter som har depression samt undersöka hur shunting och komorbiditet påverkar livskvalitet vid INPH.

I den första kohorten undersöktes kliniska och radiologiska fynd som tydde på INPH hos de patienter som blivit diagnostiserade med en TIA (från engelskans: transient ischemic attack) 2006-2008 på Norrlands Universitetssjukhus i Umeå. I den andra kohorten undersöktes konsekutivt shuntade INPH-patienter 2008-2010 från fem av sex neurokirurgiska kliniker i Sverige. De patienter som inkluderades i studien (n=176, ålder: 60-85 år, ej dementa) jämfördes med köns- och åldersmatchade kontroller från normalpopulationen (n=368, samma inklusionskriterier som för INPH-patienterna). De riskfaktorer som undersöktes var: hypertension, hyperlipidemi, diabetes, fetma, psykosociala faktorer (stress och depression), rökning, alkohol, fysisk aktivitet och diet. Även kardiovaskulära och cerebrovaskulära sjukdomar undersöktes, liksom perifer vaskulär sjukdom samt livskvalitet. Datainsamling skedde genom frågeformulär, kliniska undersökningar, mätningar, EKG och blodprov.

I den första kohorten hade 4% av TIA-patienterna kliniskt och radiologiskt verifierad INPH. I den andra kohorten var vaskulära riskfaktorer överrepresenterade hos INPH-patienterna jämfört med iv normalpopulationen. Hyperlipidemi (OR: 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), fetma (OR: 5.4, 95%CI: 2.5-11.8) och psykosociala faktorer (OR: 5.3, 95%CI: 3.2-8.9) var associerade med INPH oberoende av kön, ålder och de andra riskfaktorerna. Hypertension och fysisk inaktivitet var också associerade med INPH, dock inte oberoende av övriga riskfaktorer. Sammanlagd PAR% (från engelskans: population attributable risk %) för de här sex riskfaktorerna var 24%. INPH-patienterna hade depression i högre utsträckning än kontrollerna (46% vs. 13%, p<0.001), och depression var den viktigaste prediktorn för låg livskvalitet.

Resultaten tyder på att vaskulär sjukdom och vaskulära riskfaktorer är involverade i den patofysiologiska mekanismen vid INPH. INPH kan vara en undergrupp till vaskulär demens. En fullständig riskfaktoranalys och screening för depression bör ingå i den preoperativa utvärderingen såväl som i forskning på INPH-patienter, och ett mått på livskvalitet bör införas. Effekten av riktade insatser mot såväl vaskulära riskfaktorer som depression vid INPH bör utvärderas.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2016. 88 + 4 artiklar p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1805
Keyword
hydrocephalus, normal pressure, vascular disease, vascular risk factors, elderly, depression, case control study, epidemiology, dementia, vascular dementia, small vessel disease, cerebrovascular disease, transient ischemic attack
National Category
Cardiac and Cardiovascular Systems
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-120175 (URN)978-91-7601-471-4 (ISBN)
Public defence
2016-05-27, Bergasalen, Södra entrén, Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2016-05-12 Created: 2016-05-10 Last updated: 2016-05-26Bibliographically approved

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Israelsson, HannaCarlberg, BoLaurell, KatarinaEklund, AndersMalm, Jan
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Department of Pharmacology and Clinical NeuroscienceDepartment of Radiation SciencesDepartment of Public Health and Clinical MedicineCentre for Biomedical Engineering and Physics (CMTF)
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