umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Comorbidity and vascular risk factors  associated with idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
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 [en]
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: urn:nbn:se:umu:diva-120175ISBN: 978-91-7601-471-4 (print)OAI: oai:DiVA.org:umu-120175DiVA: diva2:927077
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
List of papers
1. Ventriculomegaly and balance disturbances in patients with TIA
Open this publication in new window or tab >>Ventriculomegaly and balance disturbances in patients with TIA
Show others...
2012 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, no 3, 163-170 p.Article in journal (Refereed) Published
Abstract [en]

Objectives -  Dilated ventricles and gait disturbances are common in the elderly, and these are also features of the treatable syndrome idiopathic normal pressure hydrocephalus (INPH). Many studies report an association between hypertension, vascular disease and INPH. The objective of this study was to study the frequency of ventriculomegaly, with or without hydrocephalic symptoms, in patients who had suffered from a transitory ischaemic attack (TIA).

Methods -  Gait, Romberg sign, tandem standing and one-leg stance were consecutively evaluated in elderly >24 h after a TIA. Ventricular size, white matter lesions and atrophy were assessed on computed tomography scans. Exclusion criteria were conditions possibly influencing the balance tests.

Results -  Seventy-six patients with TIA out of 105 were included. Ventriculomegaly [Evans Index (EI) > 0.30] was observed in 19.7% and very large ventricles (EI > 0.33) in 7.9%. Ventriculomegaly was found in 58% of the patients with a previous 'history of balance or gait disturbance', but only in 12% of those without any prior disturbance (chi-square test; P = 0.0009). Three out of 76 patients with TIA (3.9%) fulfilled both radiological and clinical criteria for 'possible INPH'.

Conclusion -  Ventriculomegaly is a common finding in elderly. One out of 20 patients with TIA may suffer from INPH, existing before and independent of the TIA diagnosis. Therefore, patients presenting with ventriculomegaly and gait/balance disturbances not attributable to other causes should be referred to a hydrocephalus centre or a neurologist with special interest in INPH.

Place, publisher, year, edition, pages
John Wiley & Sons, 2012
Keyword
cerebral ventriculomegaly, hydrocephalus, normal pressure, transient ischaemic attack, postural balance, gait
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-44948 (URN)10.1111/j.1600-0404.2011.01520.x (DOI)21554255 (PubMedID)
Available from: 2011-06-15 Created: 2011-06-15 Last updated: 2017-12-11Bibliographically approved
2. Vascular risk factors contribute to idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Open this publication in new window or tab >>Vascular risk factors contribute to idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Show others...
(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
normal pressure hydrocephalus, vascular risk factors, vascular disease
National Category
Medical and Health Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-120173 (URN)
Available from: 2016-05-10 Created: 2016-05-10 Last updated: 2017-02-06
3. Symptoms of Depression are Common in Patients With Idiopathic Normal Pressure Hydrocephalus: The INPH-CRasH Study
Open this publication in new window or tab >>Symptoms of Depression are Common in Patients With Idiopathic Normal Pressure Hydrocephalus: The INPH-CRasH Study
2016 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, no 2, 161-168 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown.

OBJECTIVE: The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls.

METHODS: INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination >=23) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as >=5 points, suspected severe depression as >=12 points). This study is part of the INPH-CRasH study.

RESULTS: One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 ± 3.7 SD, controls: 1.9 ± 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005).

CONCLUSION: Symptoms of depression are overrepresented in INPH patients compared with the population, despite treatment with a shunt. Screening for depression should be done in the evaluation of INPH patients in order to find and treat a coexisting depression.

Keyword
Case-control studies, Dementia, Depression, Depressive disorder, Follow-up studies, GDS 15, drocephalus, Normal pressure
National Category
Psychiatry Geriatrics
Identifiers
urn:nbn:se:umu:diva-116731 (URN)10.1227/NEU.0000000000001093 (DOI)000368585600001 ()26528670 (PubMedID)
Available from: 2016-02-19 Created: 2016-02-11 Last updated: 2017-11-30Bibliographically approved
4. CSF shunting improves long-term quality of life in idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
Open this publication in new window or tab >>CSF shunting improves long-term quality of life in idiopathic normal pressure hydrocephalus: the INPH-CRasH Study
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Introduction

Measurements of quality of life (QoL) are important when evaluating a surgical method. However, QoL after shunting in idiopathic normal pressure hydrocephalus (INPH) is seldom assessed. The objective of this study was to assess QoL in a large cohort of shunted INPH patients, compared to the population, and investigate which factors influence QoL in INPH.

 

Methods

All INPH patients shunted in Sweden 2008-2010 were scrutinized. Population-based controls were age- and gender-matched to the patients. One hundred and seventy-six INPH patients and 368 controls were included. QoL was assessed using the EQ5D5L instrument, measuring overall QoL and health status in five dimensions. Independency, measured by accommodation and need for in-home care, and comorbidities were assessed. Patients were followed up 6-45 months after surgery (mean follow-up time: 21 months).

 

Results

Shunted INPH patients had lower QoL than controls (p<0.001). The patients’ health status in mobility, self-care, daily activities, and anxiety/depression was worse than the controls both before and after surgery (p<0.001). Shunting improved QoL (p<0.001) and health status in all dimensions (p<0.005). The main predictors of low QoL in INPH were depression (p<0.001) and severity of gait disturbance (p=0.001). Fewer INPH patients than controls lived independently (45% vs 85%, p<0.001) Time after shunting had no influence on QoL.

 

Interpretation

Improvement in QoL after shunting in INPH is long lasting, but shunted INPH patients do not reach the same level of QoL as the population. Depression and severity of gait disturbance are the strongest predictors of low QoL in INPH. 

Keyword
normal pressure hydrocephalus, quality of life
National Category
Medical and Health Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-120174 (URN)
Available from: 2016-05-10 Created: 2016-05-10 Last updated: 2016-05-11

Open Access in DiVA

fulltext(10567 kB)178 downloads
File information
File name FULLTEXT01.pdfFile size 10567 kBChecksum SHA-512
38060ec2e0fe2503c77332de7127b83544a8ad4ad164dbc9ca9ece74308055bbd2f85204e0cc0e625bba4b4dfbf4af9c1e717e4aaa7f51316025677296b63669
Type fulltextMimetype application/pdf
spikblad(70 kB)23 downloads
File information
File name SPIKBLAD01.pdfFile size 70 kBChecksum SHA-512
2475891001cd9db5398ef903caff73f7f5e45428bff78f5c73e1848b0ccf76f813e322e788ae6dccc902734371cc9293c9497adf6b6ab25986c3706282557992
Type spikbladMimetype application/pdf

Search in DiVA

By author/editor
Israelsson Larsen, Hanna
By organisation
Department of Pharmacology and Clinical Neuroscience
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar
Total: 178 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 513 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf