Associations Between Intrathecal Levels of Vitamin D, Cytokines, and Core Biomarkers of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Several studies have examined association between vitamin D levels in serum and cognition, but little is known of vitamin D levels in cerebrospinal fluid (CSF) and association with Alzheimer's disease (AD). OBJECTIVE: In this cross-sectional, explorative study we investigated possible associations of vitamin D in CSF with biomarkers for AD, amyloid-ß, tau protein/phosphorylated tau protein in CSF, and with the cytokines IL-6, IL-8, and TNF-α in CSF in patients with cognitive impairment and cognitively healthy controls. METHODS: We included 100 outpatients ≥65 years referred for assessment of cognitive impairment and 76 age- and sex-matched cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D), amyloid-ß, tau protein and phosphorylated tau protein, as well as IL-6, IL-8, and TNF-α, were analyzed in CSF in both groups. RESULTS: Higher levels of 25(OH)D in CSF in all groups together were associated with lower levels of tau protein (p = 0.01) and phosphorylated tau protein (p = 0.005). We found no association between 25(OH)D levels in CSF and pathological levels of amyloid-ß in CSF nor levels of IL-6 or TNF-α in CSF. Higher levels of 25(OH)D in CSF were associated with higher levels of IL-8 in CSF (p = 0.002). However, vitamin D explained only 6% of variance in IL-8. There was no significant difference between the patient groups and the control group regarding the association between 25(OH)D in CSF and any of the three cytokines in CSF. CONCLUSION: Participants with higher CSF levels of 25(OH)D exhibited reduced CSF levels of tau protein and phosphorylated tau protein.

Vitamin D in Alzheimer's Disease: Low Levels in Cerebrospinal Fluid Despite Normal Amounts in Serum.

BACKGROUND: Vitamin D insufficiency has been suggested as a dementia risk factor. OBJECTIVE: In this cross-sectional, explorative study we investigated whether levels of vitamin D in cerebrospinal fluid (CSF) are lower in patients with positive biomarkers of Alzheimer's disease (AD) compared to cognitively healthy controls and whether polymorphisms of the vitamin D receptor (VDR) gene, FokI, BsmI, ApaI, and TaqI, are associated with levels of vitamin D in CSF and cognition. METHODS: We included 100 patients≥65 years assessed for cognitive impairment and 76 cognitively healthy controls. Levels of 25-hydroxyvitamin D (25(OH)D) in both serum and CSF, and VDR polymorphisms were analyzed. RESULTS: The mean level of 25(OH)D in serum was 78.6 (SD 28.9) nmol/l. While serum levels of 25(OH)D were not significantly different between the groups, CSF levels of 25(OH)D were significantly lower in patients with positive AD core biomarkers (p = 0.001) compared to patients without such biomarkers. Individuals with the BsmI major homozygote genotype had significantly lower results on a 10-word delayed recall test (p = 0.044) and verbal fluency test (p = 0.013), and individuals with the TaqI major homozygote genotype had significantly lower results on a verbal fluency test (p = 0.030) compared to individuals with the corresponding minor homozygote genotype. CONCLUSION: Patients with positive AD core biomarkers have low CSF levels of 25(OH)D, despite sufficient serum levels. CSF levels of 25(OH)D do not seem to be affected by any of the four VDR gene polymorphisms. TaqI and BsmI major homozygote genotypes might be at increased risk for development of cognitive decline.

Vitamin D Levels, APOE Allele, and MRI Volumetry Assessed by NeuroQuant in Norwegian Adults with Cognitive Symptoms.

BACKGROUND: Allele ɛ4 of the apolipoprotein (APOE∈4) gene is the strongest known genetic risk factor for late-onset sporadic Alzheimer's disease. A possible relationship between vitamin D and APOE is not yet clear. OBJECTIVE: In this exploratory, cross-sectional study, we examined the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and brain volumes and the associations of both serum levels of 25(OH)D and APOE polymorphism to brain volumes in 127 persons (mean age 66 years) with cognitive symptoms. METHODS: All subjects were examined with fully automated software for MRI volumetry, NeuroQuant. RESULTS: After adjustment for relevant covariates, higher serum 25(OH)D levels were associated with greater volumes of cortical gray matter on both left (p = 0.02) and right (p = 0.04) sides. When both 25(OH)D levels and APOE genotype were used as the main covariates, no significant associations were found between vitamin D level and brain volume in any of the 11 brain regions. In adjusted models, only homozygous but not heterozygous APOE∈4 allele carriers had significantly larger inferior lateral ventricles (p = 0.003) and smaller hippocampal volume (p = 0.035) than those without ɛ4. Homozygous APOE∈4 carriers also had significantly higher vitamin D levels (p = 0.009) compared to persons without the APOE∈4 allele. CONCLUSION: Higher vitamin D levels might have a preserving effect on cortical grey matter volume.

Progressive resistance training for community-dwelling women aged 90 or older; a single-subject experimental design.

PURPOSE: To examine the effect and feasibility of a 12-week programme of progressive resistance exercise on a group of nonagenarian (≥90 years) community-dwelling women. METHOD: An A-B single-subject experimental design was applied. Visual analyses were used for estimating the effect of the intervention. Outcome measurements were: Timed Up and Go (TUG), comfortable walking speed and 30-s chair stands. The programme comprised four exercises, following the principle of overload, aiming at improving strength in the main muscle groups. Feasibility of the progressive resistance intervention was assessed by recording the recruitment of participants, adherence to the intervention and adverse events. RESULTS: Twenty-seven women were invited; eight women aged 90 and above agreed to participate and six completed the study. They suffered from one to 10 chronic medical conditions. All improved their performance in the TUG test. Five of the six participants achieved a higher walking speed (11-59%) and four of them improved on the 30-s chair-stand test with five to 10 stands. No major adverse events were reported. CONCLUSION: Progressive resistance training was a safe and efficient method to enhance mobility and increase lower body strength in this heterogeneous group of nonagenarian community-dwelling women. IMPLICATIONS FOR REHABILITATION: Progressive resistance (PRT) training was found to be a safe and efficient method to enhance mobility and increase lower body strength in a group of community-dwelling women 90+. Participants with the poorest initial functional performance had great benefits, and the improvements appeared already after a few weeks of PRT. PRT might be useful in the rehabilitation field and could be implemented in facilities such as day care and senior centres frequented by very old persons with mobility limitations.

Physical performance as long-term predictor of onset of activities of daily living (ADL) disability: a 9-year longitudinal study among community-dwelling older women.

Disability in ADL of aging women is an important public health concern. It is thus of interest to identify modifiable factors underlying onset of ADL disability. We assessed whether three physical performance-based measurements could predict ADL disability 9 years later. The participants were 113 non-disabled community-dwelling women with a mean age of 79.5 years at baseline. The baseline examinations of physical performance were: functional reach, climbing steps and comfortable walking speed. ADL disability was defined as need of personal assistance in at least one of five basic ADL items. The participants were followed for 9 years. Logistic regression models were fitted for each of the physical performance measurements together with the covariates in relation to ADL disability. At follow-up 25.7% were disabled in ADL. All three performance measurements were significantly associated with the onset of ADL disability at 9 years of follow-up, however, only walking speed remained significantly related to onset of ADL disability, when all three performance measurements were included in the same model. In conclusion all the three performance measurements were related to onset of ADL disability, with walking speed having the strongest predictive value. Systematic screening based on walking speed measurements of non-disabled older women might help health professionals to identify those at risk of ADL disability and introduce preventive measures in time.

Poststroke urinary incontinence: one-year outcome and relationships with measures of attentiveness.

OBJECTIVES: To investigate the prognostic effect of poststroke urinary incontinence (UI) on 1-year outcome in relation to measurements of attention and mental processing speed. DESIGN: Prospective observational study. SETTING: Geriatric department (stroke and rehabilitation unit) in a university hospital. PARTICIPANTS: Two hundred thirty-five previously continent patients (median age 78) with an acute stroke. MEASUREMENTS: Clinical stroke syndromes, subtypes of UI, pre- and poststroke cognitive function and activities of daily living, computerized assessment of attention and processing speed for 110 of the participants, mortality and accommodation at 1 year. RESULTS: One hundred seventy patients remained continent, and 65 developed UI (27 with urge UI, 38 with UI with impaired awareness of the need to void (IA-UI). Patients with urge UI had poorer power of attention and speed of memory than continent patients but similar continuity of attention (P<.001, .001, and .07, respectively). Patients with IA-UI performed poorer in all categories than continent and patients with urge UI (all P<.01). In regression analyses, IA-UI was the strongest predictor of mortality and nursing home residence after 1 year (odds ratio=15.7, 95% confidence interval=3.6-69.7). When deaths were excluded, IA-UI and continuity of attention remained independent risk factors. CONCLUSION: Patients with poststroke UI are less attentive than continent patients. Those with IA-UI perform poorest. Sustained attention seems important for outcome and should be taken more into account in the rehabilitation process. In patients who recognize their incontinence, attention-focused training might be the most effective measure of reestablishing bladder control.

[Incontinence after stroke]. / Inkontinens etter hjerneslag.

BACKGROUND: Urinary and fecal incontinence can be a consequence of cerebral stroke. This article aims to give an overview of incidence, prevalence, risk factors, natural course and management of stroke-related incontinence. METHODS: MEDLINE search in relevant literature during the last 15 years, and own clinical and research experience. RESULTS AND CONCLUSIONS: Stroke-related incontinence is a frequent and bothersome symptom and a sign of a bad prognosis. Despite a certain spontaneous remission rate during the first year after onset of stroke, a considerable number of patients will have chronic problems. Many factors affect bladder and bowel function, and several of them are often present in the same individual. Keeping a record of natural functions and knowledge of incontinence is a prerequisite for all treatment. Impaired central inhibition of the micturition reflex is one important cause of urinary incontinence. Failure of certain cognitive functions probably has the greatest negative impact on prognosis. Even though established therapies for some urinary incontinence types have not been tested specifically in stroke patients, they may have effect and should be tried. Very little is known about post-stroke fecal incontinence. Patients with pre-existing incontinence should be offered help if they have not yet had a proper assessment and if they are motivated for it. There is a considerable need for further research in the field.

Post-stroke urinary incontinence with impaired awareness of the need to void: clinical and urodynamic features.

OBJECTIVE: To describe a clinical subtype of urinary incontinence (UI) after a stroke, i.e. with impaired awareness of the need to void (IA-UI), and to compare it to urge UI after a stroke for the risk factors and medium-term outcome. PATIENTS AND METHODS: In a consecutive sample of 315 hospitalized stroke patients who were clinically stable and able to communicate, 65 with UI were identified (27 urge UI, 38 IA-UI). All had a comprehensive clinical assessment and cerebral computed tomography (CT). Cysto-urethrometry was performed in seven patients with IA-UI. RESULTS: Of the 38 patients with IA-UI, 16 were partially aware of leakage, but not of bladder fullness; the remaining 22 denied leakage. Patients with IA-UI were more functionally impaired (P=0.001), had more visible new CT lesions (24 of 38 vs 10 of 27, P=0.04) and less frontal lobe involvement (seven of 24 vs seven of 10, P=0.05) than those with urge UI. Ten of 12 patients with parietal lobe involvement denied leakage; no particular lesion pattern was found in those with partial awareness. Two patients had normal cysto-urethrometry, four showed terminal detrusor overactivity, and one had an incompetent urethral closure mechanism. In all, bladder sensation was reduced or absent. Only two of the surviving patients had regained continence after 1 year, whereas half of those with urge UI had become continent. CONCLUSION: IA-UI after a stroke differs from urge UI in clinical and prognostic respects, and probably reflects greater brain damage. It might explain the prognostic importance of stroke-related UI. There are various urodynamic patterns. Patients with better preserved insight might benefit from early awareness training and even from additional medical treatment if bladder overactivity is present; this needs further investigation.

[Rehabilitation integrated in acute medical treatment]. / Rehabilitering integrert i akuttbehandling av sykdom.

BACKGROUND: Rehabilitation integrated in acute medical treatment is of great importance to patients with acute cerebral stroke and to frail elderly people admitted to hospital with acute medical conditions or fractures. We will focus on the latter group, which receives the least attention, but steadily increases. METHODS: MEDLINE-search for relevant literature published during the last 15 years, and own clinical experience. RESULTS AND CONCLUSIONS: Results from randomized clinical studies indicate that early geriatric rehabilitation, integrated in the acute treatment of elderly frail patients with acute diseases or hip fractures, is more effective than treatment in general medical or orthopedic wards. Geriatric intervention does not seem to increase costs. The beneficial effects consist of reduced incidence, duration and severity of delirium; fewer iatrogenic complications, better functional capacity and in some studies reduced mortality without increasing the need for institutionalization. Prerequisites for success are adequate patient selection and dedicated geriatric and rehabilitation units with full treatment responsibility. Up to 2050, there will be a dramatic increase in the number of elderly in Norway. Restructuring and reorganization of medical and orthopedic hospital departments are some of the measures required to meet this challenge.

Prognostic significance of micturition disturbances after acute stroke.

OBJECTIVES: To investigate the prevalence, incidence, clinical types, and prognostic effect of micturition disturbances in acute stroke. DESIGN: Prospective observational study. SETTING: Geriatric department (stroke and rehabilitation unit) in a community hospital (acute phase); outpatient clinic, patients' own homes, or nursing homes (3 months follow-up). PARTICIPANTS: Three hundred fifteen patients (mean age 77) with acute first-ever or recurrent stroke consecutively admitted to the hospital stroke unit. MEASUREMENTS: Premorbid basic and instrumental activities of daily living (ADLs) and mental functioning; comorbidity; previous and actual micturition symptoms; stroke syndromes; medication use; and poststroke mobility, ADLs, and cognition. RESULTS: One hundred forty-seven patients (46%) had preexisting micturition disturbances (urinary incontinence (UI), n = 98; urgency/frequency, n = 37; voiding difficulties, n = 12). Seventy-eight developed new symptoms (UI, n = 65; urgency/frequency, n = 4; sustained retention, n = 9). There were two UI types: urge UI (n = 27) and UI with impaired awareness of bladder needs (IA UI, n = 38). In regression analyses, IA UI was the only micturition disturbance predicting mortality and need for nursing home care at 3 months (odds ratio (OR) = 27.5, 95% confidence interval (CI) = 7.0-108.2), together with poor mobility (OR = 8.2, 95% CI = 2.6-26.2), and partial or total anterior circulation stroke type (OR = 3.6, 95% CI = 1.4-9.0). CONCLUSION: New-onset poststroke UI with impaired awareness of bladder needs is a strong and independent risk factor for poor outcome at 3 months. This probably reflects more serious brain damage, affecting sustained attention and information processing. Valid clinical tools to detect such dysfunction in stroke victims are needed. Clinical classification of poststroke UI is likely to improve management.

[Recurrent falls in the elderly]. / Falltendens hos gamle.

BACKGROUND: Approximately 30% of community-dwelling elderly people in developed countries fall at least once each year. Although only 10% of falls lead to serious injuries, these represent a considerable share of all injury-related hospital admissions, with high mortality and morbidity and high health care costs. Early detection of persons at risk and effective intervention measures are needed. The article gives an overview of current knowledge in this field. METHODS: A limited literature search (1989-2001) and a telephone survey among all geriatric units in Norway. RESULTS: Recurrent falls are a multifactorial problem requiring a multifactorial intervention strategy at any care level and between levels. Exercise/balance training and hip protectors seem to be the most effective measures in preventing falls and fall injuries. INTERPRETATION: Feasible selection criteria, good cooperation routines and knowledge of local resources are important. Awareness of the problem is needed not only in geriatricians, but all health professionals caring for elderly patients.

Prediction of long-term functional outcome after stroke rehabilitation.

OBJECTIVE: To find patient characteristics in the early post stroke phase that could predict three years functional outcome. DESIGN: Prospective study. SETTING: In-hospital rehabilitation department (admission and discharge). Outpatient department one and three years post stroke. SUBJECTS: One hundred and forty-two stroke patients (56% women), median age 75 years. MAIN OUTCOME MEASURES: Barthel Index (BI) score; BI score change; accommodation status; Rankin scale score; and Frenchay Activities Index (FAI) score, all registered three years post stroke. RESULTS: The percentages of patients still living at home after one and three years were 88% and 83%, respectively. Twenty per cent of the patients had deteriorated according to the BI after three years, mostly due to recurrent strokes (odds ratio (OR) 10.3; 95% confidence interval (CI) 3.0-35.5) and co-morbidity with other disabling disorders (OR 3.9; CI 1.1-13.5). Co-morbidity also emerged as an important risk factor for dependency according to BI score (OR 8.8; Cl 2.4-32.1) as well as for a poor FAI score (OR 4.9; CI 1.9-13.0). BI in the early phase was the strongest predictor for long-term functional outcome. Urinary incontinence emerged as a risk factor for nursing home placement after three years (OR 3.2; CI 0.9-11.3). Cognitive dysfunction was a risk factor for poor FAI scoring (OR 2.7; CI 1.0-7.0). CONCLUSIONS: After stroke rehabilitation, concomitant chronic disabling disorders and recurrent strokes seem to play an important role regarding dependency, handicap and long-term functional decline.