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Israelsson Larsen, HannaORCID iD iconorcid.org/0000-0002-0125-9589
Alternative names
Publications (10 of 17) Show all publications
Larsson, J., Hansson, W., Israelsson Larsen, H., Koskinen, L.-O. D., Eklund, A. & Malm, J. (2025). Higher-level gait disorders: a population-based study on prevalence, quality of life, depression and confidence in gait and balance. BMJ Neurology Open, 7(1), Article ID e000992.
Open this publication in new window or tab >>Higher-level gait disorders: a population-based study on prevalence, quality of life, depression and confidence in gait and balance
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2025 (English)In: BMJ Neurology Open, ISSN 2632-6140, Vol. 7, no 1, article id e000992Article in journal (Refereed) Published
Abstract [en]

Background: Higher-level gait disorders (HLGDs) are slow, unsteady neurological GDs in older people. GDs can reduce quality of life (QoL) and cause depression. This has not been investigated in HLGD even though some HLGD causes are treatable, potentially affecting associated problems. We aimed to investigate gait and balance confidence, depressive symptoms and QoL in HLGD.

Methods: In a population (n=3769, 65-84y), 798 reported gait impairment (questionnaire) and were clinically examined together with 249 age- and sex-matched controls. Gait property groups were formed: 'HLGD', 'other neurological GD', 'non-neurological GD' or 'no GD'. Swedish Falls Efficacy Scale (FES(S)), Modified Gait Efficacy Scale (mGES), Euro Quality of Life 5-Dimension 5-Level index, Euro Quality of Life Visual Analogue Scale (EQ VAS) and Geriatric Depression Scale-15 (GDS-15) were compared.

Results: In the general population, 38% had GDs, of which 16% (n=87/561) were HLGDs, giving an HLGD prevalence of 5.8%; 26% (n=145/561) were other neurological GDs; and 59% (n=329/561) non-neurological GDs. HLGD had more depressive symptoms than non-neurological GD and no GD (GDS-15 HLGD, 3.9 +/- 3.4; non-neurological GD, 2.5 +/- 2.8; no GD, 1.4 +/- 2.0; p<0.05), lower EQ VAS (HLGD, 63 +/- 17; non-neurological GD, 71 +/- 18; no GD, 82 +/- 14; p<0.001), lower gait confidence (mGES HLGD, 60 +/- 22; non-neurological GD, 74 +/- 21; no GD, 90 +/- 13; p<0.001) and lower balance confidence (FES(S) HLGD, 93 +/- 32; non-neurological GD, 111 +/- 25; no GD, 124 +/- 13; p<0.001).

Conclusions: HLGDs are common and associated with reduced QoL, reduced confidence in gait and balance, and depressive symptoms, emphasising awareness of mental health among older people with slow unsteady gait.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2025
Keywords
Gait, Quality of life, Depression, epidemiology, movement disorders
National Category
Neurosciences Psychiatry
Research subject
Geriatrics; Neurology; Psychiatry
Identifiers
urn:nbn:se:umu:diva-243350 (URN)10.1136/bmjno-2024-000992 (DOI)001445007200001 ()40092839 (PubMedID)2-s2.0-105025048113 (Scopus ID)
Funder
Swedish Foundation for Strategic ResearchSwedish Heart Lung Foundation, 19-21, 20180513The Swedish Brain Foundation, F2022-0216
Available from: 2025-08-20 Created: 2025-08-20 Last updated: 2026-01-19Bibliographically approved
Larsson, J., Israelsson Larsen, H., Eklund, A., Lundin-Olsson, L. & Malm, J. (2021). Falls and Fear of Falling in Shunted Idiopathic Normal Pressure Hydrocephalus: The Idiopathic Normal Pressure Hydrocephalus Comorbidity and Risk Factors Associated With Hydrocephalus Study. Neurosurgery, 89(1), 122-128
Open this publication in new window or tab >>Falls and Fear of Falling in Shunted Idiopathic Normal Pressure Hydrocephalus: The Idiopathic Normal Pressure Hydrocephalus Comorbidity and Risk Factors Associated With Hydrocephalus Study
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2021 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 89, no 1, p. 122-128Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Gait and balance impairment are typical symptoms of idiopathic normal pressure hydrocephalus (INPH), implicating that falls may afflict these patients.

OBJECTIVE: To investigate falls, related injuries, and associated psychological features, before and after shunt surgery for INPH and compared to the general population.

METHODS: The study included 176 patients shunted for INPH and 368 age- and sex-matched controls. Falls, fear of falling (FOF), fall-related injuries (mild-severe), confidence in avoiding falls (Swedish Falls Efficacy Scale (FES(S)), quality of life (QoL; EuroQoL 5-dimension 5 level instrument), and symptoms of depression (Geriatric Depression Scale 15) were investigated. Pre- and postoperative observational times were 12 mo before surgery and 21 mo after (mean). Recurrent fallers fell ≥2 times.

RESULTS: More INPH patients than controls were recurrent fallers (67% vs 11%; P < .001). They feared falling more often (FOF, mean ± standard deviation: 3.3 ± 1.1 vs 1.6 ± 0.9; P < .001) and had lower confidence in avoiding falls (FES(S) 78 ± 40 vs 126 ± 14; P < .001). After surgery, INPH patients improved in all parameters but they did not reach the levels of the controls. Among fallers there was no difference between patients and controls in the severity of injuries suffered. Low QoL and symptoms of depression were more common among recurrent fallers than one-time or nonfallers in both shunted patients and controls (P ≤ .001).

CONCLUSION: Falls, FOF, and low confidence in avoiding falls are considerable problems in INPH that may be reduced by shunt surgery. We suggest that remaining risk of falling and preventative measures are routinely considered in postoperative follow-ups and rehabilitation planning.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
Accidental falls, Case-control studies, Cognitive dysfunction, Depression, Gait disorders, neurologic, Quality of life, Ventriculoperitoneal shunt
National Category
Neurology Geriatrics
Identifiers
urn:nbn:se:umu:diva-185377 (URN)10.1093/neuros/nyab094 (DOI)000671548600056 ()33830219 (PubMedID)2-s2.0-85108303856 (Scopus ID)
Funder
Region Västerbotten, 7003576
Available from: 2021-06-29 Created: 2021-06-29 Last updated: 2023-03-24Bibliographically approved
Israelsson, H., Eklund, A. & Malm, J. (2020). Cerebrospinal Fluid Shunting Improves Long-Term Quality of Life in Idiopathic Normal Pressure Hydrocephalus. Neurosurgery, 86(4), 574-582
Open this publication in new window or tab >>Cerebrospinal Fluid Shunting Improves Long-Term Quality of Life in Idiopathic Normal Pressure Hydrocephalus
2020 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 86, no 4, p. 574-582Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The short- and long-term impact of cerebrospinal fluid shunting on quality of life (QoL) in idiopathic normal pressure hydrocephalus (INPH) is poorly understood.

OBJECTIVE: To investigate QoL in shunted INPH patients compared to the population and to investigate which factors influence QoL in INPH.

METHODS: INPH patients consecutively shunted in Sweden during 2008-2010 were scrutinized. Population-based controls were age- and sex-matched to the patients. Included participants were the following: 176 INPH patients and 368 controls. QoL was assessed using the EuroQol 5-dimension 5-level (EQ5D5L) instrument, which measures overall QoL and health status in 5 dimensions. Independency (accommodation and/or need for in-home care) and comorbidities were assessed. Patients were followed up 6-45 mo after surgery (mean follow-up time: 21 mo).

RESULTS: Shunting improved QoL (P < .001) and health status in all dimensions (P < .005). Shunted INPH patients had lower QoL than controls (P < .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 < .001). The main predictors of low QoL in INPH were symptoms of depression (P < .001) and severity of gait disturbance (P = .001). Fewer INPH patients than controls lived independently (45% vs 85%, P < .001). Time after shunting had no influence on QoL.

CONCLUSION: QoL remains improved in shunted INPH patients at a mean follow-up time of 21 mo, but the patients do not reach the same QoL as the population. Symptoms of depression and severity of gait disturbance are the strongest predictors of low QoL in INPH.

Place, publisher, year, edition, pages
Oxford University Press, 2020
Keywords
Case-control studies, Dementia, Depression, Follow-up studies, Hydrocephalus, INPH CRASH, Normal pressure, Quality of life
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-167309 (URN)10.1093/neuros/nyz297 (DOI)000536480800028 ()31504827 (PubMedID)2-s2.0-85081900509 (Scopus ID)
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2020-01-15 Created: 2020-01-15 Last updated: 2023-03-24Bibliographically approved
Israelsson Larsen, H., Larsson, J., Eklund, A. & Malm, J. (2020). Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus: review of the INPH-CRasH study. Neurosurgical Focus, 49(4), Article ID E8.
Open this publication in new window or tab >>Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus: review of the INPH-CRasH study
2020 (English)In: Neurosurgical Focus, ISSN 1092-0684, Vol. 49, no 4, article id E8Article, review/survey (Refereed) Published
Abstract [en]

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a shunt that drains CSF. The cause of the disease is unknown, but a vascular pathway has been suggested. The INPH-CRasH (Comorbidities and Risk Factors Associated with Hydrocephalus) study was a modern epidemiological case-control study designed to prospectively assess parameters regarding comorbidities and vascular risk factors (VRFs) for INPH, quality of life (QOL), and adverse events in patients with shunted INPH. The objective of this review was to summarize the findings of the INPH-CRasH study.

METHODS: VRFs, comorbidities, QOL, and adverse events were analyzed in consecutive patients with INPH who underwent shunt placement between 2008 and 2010 in 5 of 6 neurosurgical centers in Sweden. Patients (n = 176, within the age span of 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 patients with INPH). Assessed parameters were as follows: hypertension; diabetes; obesity; hyperlipidemia; psychosocial factors (stress and depression); smoking status; alcohol intake; physical activity; dietary pattern; cerebrovascular, cardiovascular, or peripheral vascular disease; epilepsy; abdominal pain; headache; and clinical parameters before and after surgery. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG studies, and blood samples.

RESULTS: Four VRFs were independently associated with INPH: hyperlipidemia, diabetes, obesity, and psychosocial factors. Physical inactivity and hypertension were also associated with INPH, although not independently from the other risk factors. The population attributable risk percent for a model containing all of the VRFs associated with INPH was 24%. Depression was overrepresented in patients with INPH treated with shunts compared to the controls (46% vs 13%, p < 0.001) and the main predictor for low QOL was a coexisting depression (p < 0.001). Shunting improved QOL on a long-term basis. Epilepsy, headache, and abdominal pain remained common for a mean follow-up time of 21 months in INPH patients who received shunts.

CONCLUSIONS: The results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for QOL should probably be included in the workup of patients with INPH. The effect of targeted interventions against modifiable VRFs and antidepressant treatment in INPH patients should be evaluated. Seizures, headache, and abdominal pain should be inquired about at postoperative follow-up examinations.

Place, publisher, year, edition, pages
Rolling Meadows: American Association of Neurological Surgeons, 2020
Keywords
normal pressure hydrocephalus, vascular disease, vascular risk factors, outcome of surgery, adverse events, quality of life
National Category
Neurology Surgery
Identifiers
urn:nbn:se:umu:diva-176784 (URN)10.3171/2020.7.FOCUS20466 (DOI)000581702500008 ()33002861 (PubMedID)2-s2.0-85092455590 (Scopus ID)
Available from: 2020-11-26 Created: 2020-11-26 Last updated: 2023-03-23Bibliographically approved
Andrén, K., Wikkelsø, C., Sundström, N., Israelsson, H., Agerskov, S., Laurell, K., . . . Tullberg, M. (2020). Survival in treated idiopathic normal pressure hydrocephalus. Journal of Neurology, 267(3), 640-648
Open this publication in new window or tab >>Survival in treated idiopathic normal pressure hydrocephalus
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2020 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 267, no 3, p. 640-648Article in journal (Refereed) Published
Abstract [en]

Objective: To describe survival and causes of death in 979 treated iNPH patients from the Swedish Hydrocephalus Quality Registry (SHQR), and to examine the influence of comorbidities, symptom severity and postoperative outcome.

Methods: All 979 patients operated for iNPH 2004–2011 and registered in the SHQR were included. A matched control group of 4890 persons from the general population was selected by Statistics Sweden. Data from the Swedish Cause of Death Registry was obtained for patients and controls.

Results: At a median 5.9 (IQR 4.2–8.1) year follow-up, 37% of the iNPH patients and 23% of the controls had died. Mortality was increased in iNPH patients by a hazard ratio of 1.81, 95% CI 1.61–2.04, p < 0.001. More pronounced symptoms in the preoperative ordinal gait scale and the Mini-mental State Examination were the most important independent predictors of mortality along with the prevalence of heart disease. Patients who improved in both the gait scale and in the modified Rankin Scale postoperatively (n = 144) had a similar survival as the general population (p = 0.391). Deaths due to cerebrovascular disease or dementia were more common in iNPH patients, while more controls died because of neoplasms or disorders of the circulatory system.

Conclusions: Mortality in operated iNPH patients is 1.8 times increased compared to the general population, a lower figure than previously reported. The survival of iNPH patients who improve in gait and functional independence is similar to that of the general population, indicating that shunt surgery for iNPH, besides improving symptoms and signs, can normalize survival.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2020
Keywords
Hydrocephalus, Gait disorders, Cognitive disorders, Prognosis, Cohort studies
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-165753 (URN)10.1007/s00415-019-09598-1 (DOI)000495682300002 ()31713102 (PubMedID)2-s2.0-85075162415 (Scopus ID)
Available from: 2019-12-09 Created: 2019-12-09 Last updated: 2021-04-28Bibliographically approved
Larsson, J., Israelsson, H., Eklund, A. & Malm, J. (2018). Epilepsy, headache, and abdominal pain after shunt surgery for idiopathic normal pressure hydrocephalus: the INPH-CRasH study. Journal of Neurosurgery, 128(6), 1674-1683
Open this publication in new window or tab >>Epilepsy, headache, and abdominal pain after shunt surgery for idiopathic normal pressure hydrocephalus: the INPH-CRasH study
2018 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 128, no 6, p. 1674-1683Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Adverse events related to shunt surgery are common and might have a negative effect on outcome in patients with idiopathic normal pressure hydrocephalus (INPH). The authors' objectives were to establish the frequencies of epilepsy, headache, and abdominal pain and determine their impact on patient quality of life (QOL), in long-term follow-up after shunt surgery for INPH.

METHODS One hundred seventy-six shunt-treated patients with INPH (mean age 74 years) and 368 age- and sex-matched controls from the population were included. The mean follow-up time after surgery was 21 months (range 6-45 months). Each participant answered a questionnaire regarding present frequency and severity of headache and abdominal pain. Confirmed diagnoses of epilepsy and all prescriptions for antiepileptic drugs (AEDs) before and after shunt surgery for INPH were gathered from national registries. Equivalent presurgical and postsurgical time periods were constructed for the controls based on the date of surgery (the division date for controls is referred to as virtual surgery). All registry data covered a mean period of 6 years (range 3-8 years) before surgery/virtual surgery and 4 years (range 2-6 years) after surgery/virtual surgery. Provoked epileptic seizures were excluded. Patient QOL was assessed with the EuroQoL 5-dimension 5-level instrument.

RESULTS Epilepsy was more common in shunt-treated patients with INPH than in controls (4.5% vs 1.1%, respectively; p = 0.023), as was treatment with AEDs (14.8% vs 7.3%, respectively; p = 0.010). No difference was found between the populations before surgery/virtual surgery (epilepsy, 2.3% [INPH] vs 1.1% [control], p = 0.280; AED treatment, 8.5% [INPH] vs 5.4% [control], p = 0.235). New-onset epilepsy and new AED treatment after surgery/virtual surgery were more common in INPH (epilepsy, 2.3% [INPH] vs 0.0% [control], p = 0.011; AED, 8.5% [INPH] vs 3.3% [control], p = 0.015). At follow-up, more patients with INPH than controls experienced headache several times per month or more often (36.1% vs 11.6%, respectively; p < 0.001). Patients with INPH and unilateral headache had more right-sided headaches than controls (p = 0.038). Postural headache was experienced by 16% (n = 27 of 169) of the patients with INPH. Twenty percent (n = 35) of the patients with INPH had persistent abdominal pain. Headache was not correlated to lower QOL. The study was underpowered to draw conclusions regarding QOL in patients with INPH who had epilepsy and abdominal pain, but the finding of no net difference in mean QOL indicates that no correlation between them existed.

CONCLUSIONS Epilepsy, headache, and abdominal pain are common in long-term follow-up in patients after shunt surgery for INPH and are more common among patients with INPH than in the general population. All adverse events, including mild and moderate ones, should be considered during postoperative follow-ups and in the development of new methods for shunt placement.

Place, publisher, year, edition, pages
Rolling Meadows: American association of neurological surgeons, 2018
Keywords
hydrocephalus, normal pressure, ventriculoperitoneal shunt, postoperative complications, headache, epilepsy, abdominal pain
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-139649 (URN)10.3171/2017.3.JNS162453 (DOI)000440653000010 ()28885121 (PubMedID)2-s2.0-85048221123 (Scopus ID)
Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2022-11-22Bibliographically approved
Andrén, K., Wikkelsö, C., Sundström, N., Agerskov, S., Israelsson, H., Laurell, K., . . . Tullberg, M. (2018). Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study. Journal of Neurology, 265(1), 178-186
Open this publication in new window or tab >>Long-term effects of complications and vascular comorbidity in idiopathic normal pressure hydrocephalus: a quality registry study
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2018 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 1, p. 178-186Article in journal (Refereed) Published
Abstract [en]

Background: There is little knowledge about the factors influencing the long-term outcome after surgery for idiopathic normal pressure hydrocephalus (iNPH).

Objective: To evaluate the effects of reoperation due to complications and of vascular comorbidity (hypertension, diabetes, stroke and heart disease) on the outcome in iNPH patients, 2–6 years after shunt surgery.

Methods: We included 979 patients from the Swedish Hydrocephalus Quality Registry (SHQR), operated on for iNPH during 2004–2011. The patients were followed yearly by mailed questionnaires, including a self-assessed modified Rankin Scale (smRS) and a subjective comparison between their present and their preoperative health condition. The replies were grouped according to the length of follow-up after surgery. Data on clinical evaluations, vascular comorbidity, and reoperations were extracted from the SHQR.

Results: On the smRS, 40% (38–41) of the patients were improved 2–6 years after surgery and around 60% reported their general health condition to be better than preoperatively. Reoperation did not influence the outcome after 2–6 years. The presence of vascular comorbidity had no negative impact on the outcome after 2–6 years, assessed as improvement on the smRS or subjective improvement of the health condition, except after 6 years when patients with hypertension and a history of stroke showed a less favorable development on the smRS.

Conclusion: This registry-based study shows no negative impact of complications and only minor effects of vascular comorbidity on the long-term outcome in iNPH.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
hydrocephalus, normal pressure, dementia, gait, complications, concomitant disease, risk factors, registries
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-144413 (URN)10.1007/s00415-017-8680-z (DOI)000419777000023 ()29188384 (PubMedID)2-s2.0-85035324543 (Scopus ID)
Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2023-03-24Bibliographically approved
Bäcklund, T., Frankel, J., Israelsson, H., Malm, J. & Sundström, N. (2017). Trunk sway in idiopathic normal pressure hydrocephalus: quantitative assessment in clinical practice. Gait & Posture, 62-70, Article ID 54.
Open this publication in new window or tab >>Trunk sway in idiopathic normal pressure hydrocephalus: quantitative assessment in clinical practice
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2017 (English)In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, p. 62-70, article id 54Article in journal (Refereed) Published
Abstract [en]

Background: In diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)).

Methods: Trunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group.

Results: Preoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p < 0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p < 0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p < 0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture.

Conclusions: INPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up. 

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Idiopathic normal pressure hydrocephalus, Trunk sway, Balance, Gait, Gyroscope
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-138239 (URN)10.1016/j.gaitpost.2017.02.017 (DOI)000405044400011 ()28259041 (PubMedID)2-s2.0-85014113899 (Scopus ID)
Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2023-03-23Bibliographically approved
Israelsson, H., Carlberg, B., Wikkelsö, C., Laurell, K., Kahlon, B., Leijon, G., . . . Malm, J. (2017). Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study). Neurology, 88(6), 577-585
Open this publication in new window or tab >>Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study)
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2017 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 6, p. 577-585Article in journal (Refereed) Published
Abstract [en]

Objective: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and populationbased controls to determine the extent to which vascular disease influences INPH pathophysiology. Methods: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age-and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. Results: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [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, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. Conclusions: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
National Category
Cardiology and Cardiovascular Disease Geriatrics
Identifiers
urn:nbn:se:umu:diva-139590 (URN)10.1212/WNL.0000000000003583 (DOI)000397342100013 ()28062721 (PubMedID)2-s2.0-85011685084 (Scopus ID)
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2025-02-10Bibliographically approved
Israelsson Larsen, H. (2016). Comorbidity and vascular risk factors  associated with idiopathic normal pressure hydrocephalus: the INPH-CRasH Study. (Doctoral dissertation). Umeå: Umeå University
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. p. 88 + 4 artiklar
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1805
Keywords
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
Cardiology and Cardiovascular Disease
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: 2025-02-10Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0125-9589

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