| 1. |
- Abdullah, Laila, et al.
(författare)
-
The Influence of Baseline Alzheimer's Disease Severity on Cognitive Decline and CSF Biomarkers in the NILVAD Trial.
- 2020
-
Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the effects of a dihydropyridine calcium channel blocker nilvadipine with anti-inflammatory properties on cognition and cerebrospinal fluid (CSF) biomarkers by baseline Alzheimer's disease (AD) severity. Exploratory analyses were performed on the dataset (n = 497) of a phase III randomized placebo-controlled trial to examine the response to nilvadipine in AD subjects stratified by baseline AD severity into very mild (MMSE ≥ 25), mild (MMSE 20-24) and moderate AD (MMSE < 20). The outcome measures included total and subscale scores of the Alzheimer's Disease Assessment Scale Cognitive 12 (ADAS-Cog 12), the Clinical Dementia Rating Scale sum of boxes (CDR-sb) and the AD composite score (ADCOMS). Cerebrospinal fluid biomarkers Aβ38, Aβ40, Aβ42, neurofilament light chain (NFL), neurogranin, YKL-40, total tau and P181 tau (ptau) were measured in a subset of samples (n = 55). Regression analyses were adjusted for confounders to specifically examine the influence of nilvadipine and baseline AD severity on cognitive outcomes over 78-weeks. Compared to their respective placebo-controls, nilvadipine-treated, very mild AD subjects showed less decline, whereas moderate AD subjects showed a greater cognitive decline on the ADAS-Cog 12 test and the ADCOMS. A lower decline was observed after nilvadipine treatment for a composite memory trait in very mild AD subjects and a composite language trait in mild AD subjects. Cerebrospinal fluid Aβ42/Aβ40 ratios were increased in mild AD and decreased in moderate AD patients treated with nilvadipine, compared to their respective controls. Among moderate AD subjects, levels of ptau, total tau, neurogranin and YKL-40 increased in subjects treated with nilvadipine compared to placebo. These studies suggest that baseline AD severity influenced the treatment outcome in the NILVAD trial and that future clinical trials of nilvadipine should be restricted to mild and very mild AD patients. Trial Registration: NCT02017340 Registered 20 December 2013, https://clinicaltrials.gov/ct2/show/NCT02017340 EUDRACT Reference Number 2012-002764-27 Registered 04 February 2013, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002764-27.
|
|
| 2. |
- Bjerke, Maria, 1977, et al.
(författare)
-
Cerebrospinal Fluid Fatty Acid-Binding Protein 3 is Related to Dementia Development in a Population-Based Sample of Older Adult Women Followed for 8 Years.
- 2016
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 49:3, s. 733-741
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Increased fatty acid-binding protein 3 (FABP-3) levels have been reported in neurodegenerative diseases, including Alzheimer's disease (AD). Cerebrospinal fluid (CSF) FABP-3 has therefore been proposed as a putative marker for dementia. Population-based studies examining whether CSF FABP-3 predicts later development of dementia are lacking. OBJECTIVE: The aim of this study was to examine CSF levels of FABP-3 in relation to later development of dementia in elderly women and in relation to Aβ42, T-tau, P-tau181, and CSF: serum albumin ratio. METHODS: 86 non-demented women aged 70-84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992-93. CSF-FABP-3, Aβ42, T-tau, P-tau181, and the CSF: serum albumin ratio were measured at baseline. Participants were examined with a neuropsychiatric exam at baseline and at follow-up in 2000. Dementia was diagnosed in accordance with DSM-III-R criteria. RESULTS: Between 1992 and 2000, 8 women developed dementia (4 AD, 3 vascular dementia, 1 mixed vascular dementia and AD). Higher levels of CSF-FABP-3 at baseline were related to development of dementia (OR 1.36 CI [1.05-1.76] p=0.022) and the subtype AD (OR 1.38 CI [1.06-1.82), p=0.019) during follow-up. FABP-3 correlated with CSF T-tau (r=0.88, p< 0.001), P-tau181 (r=0.619, p< 0.001), and CSF:serum albumin ratio (r=0.233, p=0.031), but not with Aβ42 (r=-0.08, p=0.444)Conclusion: CSF FABP-3 may be an early marker for later development of dementia, probably related to neuronal degeneration, but independent of Aβ metabolism.
|
|
| 3. |
- Börjesson-Hanson, Anne, 1959
(författare)
-
Dementia and other mental disorders among 95-year olds
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to estimate the prevalence of mental disorders and age related differences in the very elderly. In addition, five-year mortality after age 95 in relation to dementia and cognitive function in non-demented, was examined. A population sample of 338 95-year olds (response rate 65%) living in Gothenburg, Sweden, was compared with 85- (N=494) and 75-year olds (N=303) from the same birth cohort. All participants were examined by psychiatrists. The assessments included the Comprehensive Psychopathological Rating Scale, cognitive tests, the Mini Mental State Examination (MMSE), medical history, physical examination and a telephone interview with a key informant. Dementia, depression, anxiety and psychosis were classified according to DSM-III-R criteria, Alzheimer?s disease according to NINCDS-ADRDA criteria and vascular dementia (VaD) according to NINDS-AIREN criteria. Two-thirds (66%) of the 95-year olds fulfilled criteria for a mental disorder. Dementia was more common (52% vs. 30%; p<0.001) and more severe in 95-year olds than in 85-year olds. Among 95-year olds, dementia was more common in women than in men (56% vs. 37%; p=0.006). The proportion of VaD was lower among 95-year olds than among 85-year olds (30% vs. 40%; p<0.001). Almost one-third (29%) of the non-demented 95-year olds had a psychiatric disorder (depression 17%, anxiety disorders 9%, psychotic disorder 7%). Psychotic symptoms among non-demented 95-year olds were not associated with other psychiatric symptoms, sensory impairments or cognitive function. The prevalence of psychiatric disorders among non-demented was higher for 85- and 95-year olds than for 75-year olds. Five-year survival after age 95 was similar in men and women, but when controlling for dementia, male sex predicted mortality. Dementia was the leading predictor for death after age 95 and attributed to 40% of deaths. For each point increase in the MMSE score among the non-demented 95-year olds, mortality decreased by 13% (RR 0.87; p<0.0002). The high prevalence of psychiatric disorders emphasizes the importance of detecting and treating psychiatric problems among the oldest old, and also the need for further research on mental health in this age group. There is a concern that psychiatric symptoms among the very old are considered ?normal for age? and therefore neglected by the patients themselves, their relatives and health care professionals.
|
|
| 4. |
- Börjesson-Hanson, Anne, 1959, et al.
(författare)
-
Five-year mortality in relation to dementia and cognitive function in 95-year-olds.
- 2007
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 69:22, s. 2069-75
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dementia is a known predictor of mortality, but most studies include small numbers of participants above age 90. The influence of dementia or cognition on mortality in this age group is therefore uncertain. OBJECTIVE: To examine 5-year mortality in relation to dementia and cognitive performance at age 95. METHODS: A population sample of 338 individuals examined at age 95 was followed to age 100. Dementia was diagnosed according to DSM-III-R criteria. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Information on severe physical disorders was obtained from the Swedish Hospital Discharge Register, and date of death from the Swedish Population Register. RESULTS: Five-year mortality was higher in 95-year-olds with dementia than in 95-year-olds without dementia (96% vs 73%; p < 0.0001), even when adjusting for severe physical disorders. A Cox regression analysis with calculation of population attributable risk (PAR), calculated from adjusted relative risks, showed that mortality was predicted by dementia (PAR 42%), cardiac disease (PAR 17%), cancer (PAR 6%), and male sex (PAR 7%), but not by stroke. Among the subjects without dementia, cognitive performance measured using the MMSE (n = 133 with complete tests; 81% of the subjects without dementia) predicted mortality. For each point increase in the MMSE, mortality decreased by 13%. CONCLUSIONS: In 95-year-olds, dementia, as well as cognitive performance in the subjects without dementia, influences mortality. When controlling for other severe medical conditions we found dementia to be the leading cause of deaths among the oldest old. The reason why dementia and cognitive function predict life expectancy requires further elucidation.
|
|
| 5. |
- Börjesson-Hanson, Anne, 1959, et al.
(författare)
-
One-Month Prevalence of Mental Disorders in a Population Sample of 95-Year Olds.
- 2011
-
Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1545-7214. ; 19:3, s. 284-91
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: To determine the 1-month prevalence of mental disorders among 95-year olds. DESIGN:: Cross-sectional population sample of 95-year olds. SETTING:: All 95-year olds born in the period 1901-1903 living in Gothenburg, Sweden, were invited. Elderly living in both community settings and nursing homes were included. PARTICIPANTS:: In total, 338 95-year olds (response rate: 65%) were examined (263 women, 75 men). MEASUREMENTS:: All participants were examined by psychiatrists using the Comprehensive Psychopathological Rating Scale and cognitive tests. Mental disorders were classified according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria. RESULTS:: Two-third of all 95-year olds had a mental disorder. In the total sample of 95-year olds, the 1-month prevalence was 52% for dementia, 8% for depression, 4% for anxiety, and 3% for psychotic disorders. Almost one-third (29%) of the nondemented 95-year olds fulfilled criteria for a psychiatric disorder: 17% had depression, 9% anxiety, and 7% psychotic disorder. CONCLUSIONS:: The combined prevalence of mental disorders was high among 95-year olds, even after excluding dementia. These findings emphasize the importance of research, care, and detection of psychiatric problems in this age group.
|
|
| 6. |
|
|
| 7. |
- Craggs, L. J. L., et al.
(författare)
-
Clusterin/Apolipoprotein J immunoreactivity is associated with white matter damage in cerebral small vessel diseases
- 2016
-
Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 42:2, s. 194-209
-
Tidskriftsartikel (refereegranskat)abstract
- AimBrain clusterin is known to be associated with the amyloid- deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing on white matter changes in small vessel diseases. MethodsPost-mortem brain tissues from the frontal or temporal lobes of a total of 70 subjects with various disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were examined using immunohistochemistry and immunofluorescence. We further used immunogold electron microscopy to study clusterin immunoreactivity in extracellular deposits in CADASIL. ResultsImmunostaining with clusterin antibodies revealed strong localization in arterioles and capillaries, besides cortical neurones. We found that clusterin immunostaining was significantly increased in the frontal white matter of CADASIL and pontine autosomal dominant microangiopathy and leukoencephalopathy subjects. In addition, clusterin immunostaining correlated with white matter pathology severity scores. Immunostaining in axons ranged from fine punctate deposits in single axons to larger confluent areas with numerous swollen axon bulbs, similar to that observed with known axon damage markers such as non-phosphorylated neurofilament H and the amyloid precursor protein. Immunofluorescence and immunogold electron microscopy experiments showed that whereas clusterin immunoreactivity was closely associated with vascular amyloid- in CAA, it was lacking within the granular osmiophilic material immunolabelled by NOTCH3 extracelluar domain aggregates found in CADASIL. ConclusionsOur results suggest a wider role for clusterin associated with white matter damage in addition to its ability to chaperone proteins for clearance via the perivascular drainage pathways in several disease states.
|
|
| 8. |
- Craggs, Lucinda, et al.
(författare)
-
Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases
- 2013
-
Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 23:5, s. 547-557
-
Tidskriftsartikel (refereegranskat)abstract
- We quantified vascular changes in the frontal lobe and basal ganglia of four inherited small vessel diseases (SVDs) including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), hereditary multi-infarct dementia of Swedish type (Swedish hMID), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Vascular pathology was most severe in CADASIL, and varied with marginally greater severity in the basal ganglia compared to the frontal lobe. The overall sclerotic index values in frontal lobe were in the order CADASIL≥HERNS>PADMAL>Swedish hMID>sporadic SVD, and in basal ganglia CADASIL>HERNS>Swedish hMID>PADMAL> sporadic SVD. The subcortical white matter was almost always more affected than any gray matter. We observed glucose transporter-1 (GLUT-1) protein immunoreactivities were most affected in the white matter indicating capillary degeneration whereas collagen IV (COL4) immunostaining was increased in PADMAL cases in all regions and tissue types. Overall, GLUT-1:COL4 ratios were higher in the basal ganglia indicating modifications in capillary density compared to the frontal lobe. Our study shows that the extent of microvascular degeneration varies in these genetic disorders exhibiting common end-stage pathologies but is the most aggressive in CADASIL.
|
|
| 9. |
- de Heus, R. A. A., et al.
(författare)
-
Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
- 2019
-
Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 8:10
-
Tidskriftsartikel (refereegranskat)abstract
- Background-Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop >= 20/>= 10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 +/- 8.2 years and mean Mini-Mental State Examination score was 20.4 +/- 3.8. Baseline blood pressure was 137.8 +/- 14.0/77.0 +/- 8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo (P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI] 1.1 [0.8-1.5], P 0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7 +/- 13.8% versus 7.3 +/- 11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.
|
|
| 10. |
- Dyer, A. H., et al.
(författare)
-
Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
- 2020
-
Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
|
|
| 11. |
- Gislason, Thorsteinn, et al.
(författare)
-
Effect of diagnostic criteria on the prevalence of frontotemporal dementia in the elderly
- 2015
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:4, s. 425-433
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Frontotemporal dementia (FTD) is believed to be rare in the elderly, and the influence of different criteria on the prevalence of FTD is unclear. METHODS: Population-based samples of 70- to 95-year-olds (n = 2462) in Gothenburg, Sweden, underwent neuropsychiatric examinations. Behavioral variant FTD (bvFTD) was diagnosed according to the International Behavioural Variant FTD Criteria Consortium (FTDC), the Frontotemporal Lobe Degeneration Consensus criteria, and the Lund-Manchester Research Criteria. A subset (n = 1074) underwent computerized tomography (CT) of the brain. RESULTS: The prevalence of bvFTD varied between 0.2% and 0.5% at age 70 to 79 years, between 2.5% and 3.6% at age 80 to 89 years, and between 1.7% and 2.2% at age 90 to 95 years. The agreement between different criteria was low to moderate (κ = 0.20-0.42). Among those with bvFTD according to FTDC, 93.3% had frontal and/or temporal lobar atrophy on CT, compared with 12.6% of those without bvFTD (P < .001). CONCLUSIONS: The prevalence of bvFTD was higher than expected in this population. To a large extent, different criteria captured different individuals.
|
|
| 12. |
- Höglund, Kina, 1976, et al.
(författare)
-
Preclinical amyloid pathology biomarker positivity: effects on tau pathology and neurodegeneration
- 2017
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n = 1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (A beta 42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of A beta 42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, A beta 40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF A beta 42 levels below 530 pg ml(-1). These individuals displayed significantly higher CSF concentrations of t-tau (P < 0.001), p-tau (181) (P < 0.001), neurogranin (P = 0.009) and FABP3 (P = 0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of A beta. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE epsilon 4 and amyloid pathology in healthy older individuals.
|
|
| 13. |
- Karlsson, Björn, 1981, et al.
(författare)
-
DSM-IV and DSM-5 Prevalence of Social Anxiety Disorder in a Population Sample of Older People
- 2016
-
Ingår i: The American journal of geriatric psychiatry. - : Elsevier BV. - 1064-7481 .- 1545-7214. ; 24:12, s. 1237-1245
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine the prevalence of social anxiety disorders (SAD) with (DSM-IV) and without (DSM-5) the person's own assessment that the fear was unreasonable, in a population sample of older adults. Further, to determine whether clinical and sociodemographic correlates of SAD differ depending on the criteria applied. Design: Cross-sectional. Setting: General population in Gothenburg, Sweden. Participants: A random population-based sample of 75- and 85-year olds (N = 1200) without dementia. Measurements: Psychiatric research nurses carried out a semi-structured psychiatric examination including the Comprehensive Psychopathological Rating Scale. DSM-IV SAD was diagnosed with the Mini International Neuropsychiatric Interview. SAD was diagnosed according to DSM-IV and DSM-5 criteria. The 6-month duration criterion in DSM-5 was not applied because of lack of information. Other assessments included the Global Assessment of Functioning (GAF), the Brief Scale for Anxiety (BSA), and the Montgomery Asberg Depression Rating Scale (MADRS). Results: The 1-month prevalence of SAD was 2.5% (N = 30) when the unreasonable fear criterion was defined in accordance with DSM-IV and 5.1% (N = 61) when the DSM-5 criterion was applied. Clinical correlates (GAF, MADRS, and BSA) were worse in SAD cases identified by either procedure compared with all others, and ratings for those reporting unreasonable fear suggested greater (albeit nonsignificant) overall psychopathology. Conclusions: Shifting the judgment of how reasonable the fear was, from the individual to the clinician, doubled the prevalence of SAD. This indicates that the DSM-5 version might increase prevalence rates of SAD in the general population. Further studies strictly applying all DSM-5 criteria are needed in order to confirm these findings.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Kern, Silke, et al.
(författare)
-
Does low-dose acetylsalicylic acid prevent cognitive decline in women with high cardiovascular risk? A 5-year follow-up of a non-demented population-based cohort of Swedish elderly women.
- 2012
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 2:5
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to examine whether low-dose acetylsalicylic acid (ASA) influences the rate of cognitive change in elderly women. Design Prospective, population-based cohort study. Setting The city of Gothenburg, Sweden, including those living in private households as well as in residential care. Participants The sample was derived from the Prospective Population Study of Women and from the H70 Birth Cohort Study in Gothenburg, Sweden. Both samples were obtained from the Swedish Population Register, based on birth date, and included 789 (response rate 71%) women aged 70–92years. After the exclusion of individuals with dementia and users of warfarin, clopidogrel or heparin at baseline, 681 women were examined. Among all participants, 95.4% (N=601) had a high cardiovascular risk (CVD), defined as 10% or higher 10-year risk of any CVD event according to the Framingham heart study and 129 used low-dose ASA (75–160mg daily) at baseline. After 5years a follow-up was completed by 489 women. Primary outcome and secondary outcome measures Cognitive decline and dementia incidence in relation to the use of low-dose ASA and cardiovascular risk factors. Cognition was measured using the Mini Mental State Examination (MMSE), word fluency, naming ability and memory word tests. Dementia was diagnosed according to the DSM-III-R criterion. As secondary outcome incidence of stroke and peptic ulcer in relation to low-dose ASA use was studied. Results Women on regular low-dose ASA declined less on MMSE at follow-up than those not on ASA. This difference was even more pronounced in those who had ASA at both examinations (p=0.004 compared with never users; n=66 vs n=338). All other cognitive tests showed the same trends. There were no differences between the groups regarding short-term risk for dementia (N=41). Conclusion Low-dose ASA treatment may have a neuroprotective effect in elderly women at high cardiovascular risk.
|
|
| 17. |
|
|
| 18. |
- Kern, Silke, et al.
(författare)
-
Lower CSF interleukin-6 predicts future depression in a population-based sample of older women followed for 17 years
- 2013
-
Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591. ; 32, s. 153-158
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6) and related proinflammatory cytokines and current and future depression in a population-based sample of older women who were followed for 17 years. Methods 83 non-demented women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF- IL-6, interleukin-1β (IL-1β), interleukin- 8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. Results At baseline, women with ongoing depression had lower levels of IL-6 (p < 0.04), IL-8 (p < 0.05) and TNF-α (p < 0.05) compared with those without depression. In women without depression at baseline, lower CSF IL-6 levels predicted depression at one or more follow-up examination (p < 0.03). Results from the generalized linear mixed logistic model using all baseline and follow-up data on depression status and Mini Mental State Examination score showed a significant relationship between IL-6 and depression (p = 0.005 OR 0.370 CI [0.184–0.744]). Conclusion Lower levels of CSF IL-6 were associated with current depression and with future depression during a follow-up of almost two decades. Our findings suggest that lower levels of CSF IL-6 may be related to depression vulnerability in later life.
|
|
| 19. |
- Kern, Silke, et al.
(författare)
-
Prevalence of preclinical Alzheimer disease Comparison of current classification systems
- 2018
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 90:19
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To determine the prevalence of preclinical Alzheimer disease (AD) according to current classification systems by examining CSF from a representative general population sample of 70-year-olds from Gothenburg, Sweden. The sample was derived from the population-based H70 Gothenburg Birth Cohort Studies in Gothenburg, Sweden. The participants (n = 322, age 70 years) underwent comprehensive neuropsychiatric, cognitive, and somatic examinations. CSF levels of beta-amyloid (A beta)(42), A beta(40), total tau, and phosphorylated tau were measured. Preclinical AD was classified according to criteria of the A/T/N system, Dubois 2016, National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, and International Working Group-2 (IWG-2) criteria. Individuals with Clinical Dementia Rating score > 0 were excluded, leaving 259 cognitively unimpaired individuals. The prevalence of amyloid pathology was 22.8%, of total tau pathology was 33.2%, and of phosphorylated tau pathology was 6.9%. With the A/T/N system, the prevalence of A+/T-/N- was 13.1%, A+/T-/N+ was 7.3%, A+/T+/N+ was 2.3%, A-/T-/N+ was 18.9%, and A-/T+/N+ was 4.6%. When the Dubois criteria were applied, the prevalence of asymptomatic at risk for AD was 36.7% and of preclinical AD was 9.7%. With the NIA-AA criteria, the prevalence of stage 1 was 13.1% and stage 2 was 9.7%. With the IWG-2 criteria, the prevalence of asymptomatic at risk for AD was 9.7%. The APOE epsilon 4 allele was associated with several of the categories. Men more often had total tau pathology, A+/T-/N+, preclinical AD according to Dubois 2016, asymptomatic at risk for AD according to the IWG-2 criteria, and NIA-AA stage 2. The prevalence of pathologic AD markers was very common (46%) in a representative population sample of 70-year-olds. The clinical implications of these findings need to be scrutinized further in longitudinal studies.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Lawlor, B., et al.
(författare)
-
NILVAD protocol: A European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease
- 2014
-
Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 4:10
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis: Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDSADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADASCog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDRsb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDRsb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination: The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peerreviewed journal. Trial registration number EUDRACT Reference Number: 201200276427.
|
|
| 23. |
- Lawlor, B., et al.
(författare)
-
Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
- 2018
-
Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 15:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated antiinflammatory and anti-tau activity in preclinical studies, properties that could have diseasemodifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged > 50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of >= 12 and < 27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease +/- specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADASCog 12 on placebo was 0.79 (95% CI, -0.07 +/- 1.64) at 13 weeks, 6.41 (5.33 +/- 7.49) at 52 weeks, and 9.63 (8.33 +/- 10.93) at 78 weeks and on nilvadipine was 0.88 (0.02 +/- 1.74) at 13 weeks, 5.75 (4.66 +/- 6.85) at 52 weeks, and 9.41 (8.09 +/- 10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease.
|
|
| 24. |
- Lesén, Eva, 1982, et al.
(författare)
-
Psychotropic drug use in relation to mental disorders and institutionalization among 95-year-olds: a population-based study.
- 2011
-
Ingår i: International psychogeriatrics. - 1741-203X. ; 23:8, s. 1270-1277
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of psychotropic drug use is high among the elderly, but research on how psychotropic drugs are used among individuals aged 90 years and older is limited. An increased knowledge on this topic may contribute to improved prescribing patterns in this vulnerable population. The aim of this study was to assess the use of psychotropic drugs in relation to mental disorders and institutionalization among 95-year-olds and to identify use of potentially inappropriate psychotropic drugs. Methods: All 95-year-olds born in 1901–1903 living in nursing homes or community settings in Gothenburg, Sweden were invited to participate. The response rate was 65% and 338 95-year-olds were examined (263 women, 75 men). Psychotropic drug use in relation to mental disorders and institutionalization was assessed. Information on drug use was collected primarily from multi-dose drug dispensing lists. Participants were examined by trained psychiatrists using the Comprehensive Psychopathological Rating Scale and a battery of cognitive tests. Dementia, depression, anxiety and psychotic disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R). Results: Sixty percent of the 95-year-old participants used psychotropic drugs; hypnotics were most common (44%). Potentially inappropriate psychotropics were observed in one third (33%). Antidepressants were used by 7% of the participants without dementia who fulfilled criteria for a depressive disorder, while 56% used hypnotics and 30% used anxiolytics. Conclusions: The high prevalence of psychotropic drug use and the nonspecific nature of these treatments among 95-year-olds indicate a need for improvement in prescribing patterns.
|
|
| 25. |
- Low, W C, et al.
(författare)
-
Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL
- 2007
-
Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 130:Part 2, s. 357-367
-
Tidskriftsartikel (refereegranskat)abstract
- Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.
|
|
| 26. |
- Mellqvist Fässberg, Madeleine, et al.
(författare)
-
Suicidal feelings in the twilight of life: a cross-sectional population-based study of 97-year-olds
- 2013
-
Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the occurrence of past month suicidal feelings in extreme old age. Further, to Design: Cross-sectional population-based study. Setting: Gothenburg, Sweden. Participants: 269 adults (197 women, 72 men) without dementia born in 1901-1909 who participated Main outcome measures: Death thoughts and suicidal feelings. The latter were rated in accordance Results: One quarter of the sample (26.7%) reported that they thought about their own death at least Conclusions: Suicidal feelings may occur outside the context of depression and disability in this age
|
|
| 27. |
|
|
| 28. |
- Olesen, Pernille J, et al.
(författare)
-
A population-based study on the influence of brain atrophy on 20-year survival after age 85.
- 2011
-
Ingår i: Neurology. - 0028-3878. ; 76:10, s. 879-86
-
Tidskriftsartikel (refereegranskat)abstract
- Individuals aged 80 years and older is the fastest growing segment of the population worldwide. To understand the biology behind increasing longevity, it is important to examine factors related to survival in this age group. The relationship between brain atrophy and survival after age 85 remains unclear.
|
|
| 29. |
- Ribbe, Mats, 1985, et al.
(författare)
-
Amyloid β42 and Total Tau Levels in Cerebrospinal Fluid Associate with Survival in an 85-Year-Old Population-Based Cohort Followed until Death
- 2019
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 47:1-2, s. 114-123
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia of Alzheimer's type (AD) is related to decreased survival. It is not clear whether also biological markers of AD are related to mortality. Low levels of amyloid beta-42 (Aβ42) and high levels of total tau (T-tau) protein in cerebrospinal fluid (CSF) are established biomarkers for AD. >bold<>italic/italic<>/bold< Our aim was to investigate whether levels of Aβ42 and T-tau are associated with survival among octogenarians independently of dementia status. >bold<>italic/italic<>/bold< Sixty-five 85-year-olds underwent lumbar puncture and were followed with repeated neuropsychiatric examinations until death.>bold<>italic< Results:>/italic<>/bold< Lower CSF Aβ42 (>italic/italic< = 0.010) and higher CSF T-tau (>italic/italic< = 0.005) at the age of 85 were associated with lower survival independently of dementia status at baseline and follow-up. Low CSF Aβ42 and high CSF T-tau were also related to baseline dementia at the age of 85 years, and lower CSF Aβ42 with increased dementia incidence during the first 3 years of follow-up. >bold<>italic/italic<>/bold< Biological markers of AD are associated with mortality in octogenarians. The reason for this needs further study. Our findings highlight the importance to consider the competing risk of death when evaluating biological markers of AD in the very old. © 2019 S. Karger AG, Basel. All rights reserved.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Skoog, Ingmar, 1954, et al.
(författare)
-
Decreasing prevalence of dementia in 85-year olds examined 22 years apart: the influence of education and stroke
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Individuals aged 80 years and older constitute the fastest growing segment of the population worldwide, leading to an expected increase in dementia cases. Education level and treatment of vascular risk factors has increased during the last decades. We examined whether this has influenced the prevalence of dementia according to DSM-III-R using population-based samples of 85-year-olds (N = 1065) examined with identical methods 1986-87 and 2008-10. The prevalence of dementia was 29.8% in 1986-87 and 21.7% in 2008-10 (OR 0.66; 95%-CI: 0.50-0.86). The decline was mainly observed for vascular dementia. The proportion with more than basic education (25.2% and 57.7%), and the prevalence of stroke (20% and 30%) increased, but the odds ratio for dementia with stroke decreased from 4.3 to 1.8 (interaction stroke*birth cohort; p = 0.008). In a logistic regression, education (OR 0.70; 95%-CI 0.51-0.96), stroke (OR 3.78; 95%-CI 2.28-6.29), interaction stroke*birth cohort (OR 0.50; 95%CI 0.26-0.97), but not birth cohort (OR 0.98; 95%-CI 0.68-1.41), were related to prevalence of dementia. Thus, the decline in dementia prevalence was mainly explained by higher education and lower odds for dementia with stroke in later born birth cohorts. The findings may be related to an increased cognitive reserve and better treatment of stroke in later-born cohorts.
|
|
| 33. |
- Skoog, Ingmar, 1954, et al.
(författare)
-
Low Cerebrospinal Fluid Aβ42 and Aβ40 are Related to White Matter Lesions in Cognitively Normal Elderly.
- 2018
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 62:4, s. 1877-1886
-
Tidskriftsartikel (refereegranskat)abstract
- Low cerebrospinal fluid (CSF) levels of Aβ42 may be the earliest manifestation of Alzheimer's disease (AD). Knowledge on how CSF Aβ interacts with different brain pathologies early in the disease process is limited. We examined how CSF Aβ markers relate to brain atrophy and white matter lesions (WMLs) in octogenarians with and without dementia to explore the earliest pathogenetic pathways of AD in the oldest old.To study CSF amyloid biomarkers in relation to brain atrophy and WMLs in 85-year-olds with and without dementia.53 octogenarians took part in neuropsychiatric examinations and underwent both a lumbar puncture and a brain CT scan. CSF levels of Aβ42 and Aβ40 were examined in relation to cerebral atrophy and WMLs. Dementia was diagnosed.In 85-year-olds without dementia, lower levels of both CSF Aβ42 and CSF Aβ40 were associated with WMLs. CSF Aβ42 also correlated with measures of central atrophy, but not with cortical atrophy. In participants with dementia, lower CSF levels of Aβ42 were related to frontal, temporal, and parietal cortical atrophy but not to WMLs.Our findings may suggest that there is an interrelationship between Aβ and subcortical WMLs in older persons without dementia. After onset of dementia, low CSF Aβ42, probably representing amyloid deposition in plaques, is associated with cortical atrophy. WMLs may be an earlier manifestation of Aβ deposition than cortical degeneration.
|
|
| 34. |
- Skoog, Johan, 1985, et al.
(författare)
-
A Longitudinal Study of the Mini-Mental State Examination in Late Nonagenarians and Its Relationship with Dementia, Mortality, and Education.
- 2017
-
Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:6, s. 1296-1300
-
Tidskriftsartikel (refereegranskat)abstract
- To examine level of and change in cognitive status using the Mini-Mental State Examination (MMSE) in relation to dementia, mortality, education, and sex in late nonagenarians.Three-year longitudinal study with examinations at ages 97, 99, and 100.Trained psychiatric research nurses examined participants at their place of living.A representative population-based sample of 97-year-old Swedes (N = 591; 107 men, 484 women) living in Gothenburg, Sweden.A Swedish version of the MMSE was used to measure cognitive status. Geriatric psychiatrists diagnosed dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Mixed models were fitted to the data to model the longitudinal relationship between MMSE score and explanatory variables.Individuals with dementia between age 97 and 100 had lower mean MMSE scores than those without dementia. Those who died during the 3-year follow-up had lower MMSE scores than those who survived. MMSE scores at baseline did not differ between those without dementia and those who developed dementia during the 3-year follow-up. Participants with more education had higher MMSE scores, but there was no association between education and linear change.MMSE score is associated with dementia and subsequent mortality even in very old individuals, although the preclinical phase of dementia may be short in older age. Level of education is positively associated with MMSE score but not rate of decline in individuals approaching age 100.
|
|
| 35. |
- Sundal, Christina, et al.
(författare)
-
Different Stages of White Matter Changes in the Original HDLS Family Revealed by Advanced MRI Techniques.
- 2014
-
Ingår i: Journal of neuroimaging : official journal of the American Society of Neuroimaging. - : Wiley. - 1552-6569. ; 24:5, s. 444-452
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The temporal evolution of white matter (WM) changes on MR examinations in hereditary diffuse leukoencephalopathy with spheroids (HDLS) is largely unknown. Our purpose was to investigate the evolution of these WM changes with diffusion weighted/tensor imaging (DWI/DTI) and MR Spectroscopy (MRS). METHODS: A newly diagnosed patient with HDLS from the original Swedish family was followed prospectively with 5 MRI as well as DWI/DTI and MRS examinations during 16 months. RESULTS: The DTI eigenvalues demonstrated changes that suggested early myelin and axonal disturbances in the normal appearing WM (NAWM). DWI/DTI showed a rim of decreased diffusion progressively expanding through the WM from the initial frontal periventricular zones, and indicated complete destruction of axons and myelin in the area behind the front. MRS findings were suggestive of axonal destruction in the NAWM. CONCLUSION: We describe HDLS changes in three temporal stages of development corresponding to lesions outside, in the vicinity of, and behind a characteristic rim centrifugally progressing from the ventricular horns. The axonal disturbances indicated by MRS changes in the NAWM support a primary axonal degeneration, as proposed in the original HDLS report, rather than axonal degeneration secondary to demyelination. These findings could help in differential diagnosis of HDLS.
|
|
| 36. |
- Sundal, Christina, et al.
(författare)
-
MRI characteristics and scoring in HDLS due to CSF1R gene mutations.
- 2012
-
Ingår i: Neurology. - 1526-632X. ; 79:6, s. 566-74
-
Tidskriftsartikel (refereegranskat)abstract
- To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5.
|
|
| 37. |
- Sundal, Christina, et al.
(författare)
-
Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
- 2013
-
Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020. ; 19:10, s. 869-877
-
Tidskriftsartikel (refereegranskat)abstract
- Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by noninflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11). We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.
|
|
| 38. |
- Sundal, Christina, et al.
(författare)
-
Update of the original HDLS kindred: divergent clinical courses.
- 2012
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 126:1, s. 67-75
-
Tidskriftsartikel (refereegranskat)abstract
- Sundal C, Ekholm S, Nordborg C, Jönsson L, Börjesson-Hanson A, Lindén T, Zetterberg H, Viitanen M, Andersen O. Update of the original HDLS kindred: divergent clinical courses. Acta Neurol Scand: 2012: 126: 67-75. © 2011 John Wiley & Sons A/S. Background- Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown. Methods- We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone-interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied. Results- Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1. Conclusions- Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants.
|
|
| 39. |
- Thorvaldsson, Valgeir, 1976, et al.
(författare)
-
Nonlinear blood pressure effects on cognition in old age: separating between-person and within-person associations.
- 2012
-
Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 27:2, s. 375-383
-
Tidskriftsartikel (refereegranskat)abstract
- Midlife hypertension is associated with increased risk of cognitive impairment in later life. The association between blood pressure (BP) in older ages and cognition is less clear. In this study we provide estimates of between-person and within-person associations of BP and cognition in a population-based sample (N = 382) followed from age 70 across 12 occasions over 30 years. Between-person associations refer to how individual differences in BP relates to individual differences in cognition. Within-person associations refer to how individual and time specific changes in BP relate to variation in cognition. Hierarchical linear models were fitted to data from three cognitive measurements (verbal ability, spatial ability, and perceptual speed) while accounting for demographic and health-related covariates. We found consistent nonlinear between-person associations between diastolic BP (DBP) and cognition, such that both low (<75 mmHg) and high (>95 mmHg) pressure were associated with poorer cognition. Within-person decreases in systolic BP (SBP) and DBP were associated with decreases in perceptual speed. Notably, between-person and within-person estimates did not reveal similar associations, suggesting the need to separate the two effects in the analysis of associations between BP and cognition in old age. (PsycINFO Database Record (c) 2011 APA, all rights reserved).
|
|
| 40. |
- Thorvaldsson, Valgeir, 1976, et al.
(författare)
-
Onset and rate of cognitive change before dementia diagnosis: findings from two Swedish population-based longitudinal studies
- 2011
-
Ingår i: Journal of the International Neuropsychological Society. - 1469-7661 .- 1355-6177. ; 17:1, s. 154-62
-
Tidskriftsartikel (refereegranskat)abstract
- We used data from two population-based longitudinal studies to estimate time of onset and rate of accelerated decline across cognitive domains before dementia diagnosis. The H70 includes an age-homogeneous sample (127 cases and 255 non-cases) initially assessed at age 70 with 12 follow-ups over 30 years. The Kungsholmen Project (KP) includes an age-heterogeneous sample (279 cases and 562 non-cases), with an average age of 82 years at initial assessment, and 4 follow-ups spanning 13 years. We fit mixed linear models to the data and determined placement of change points by a profile likelihood method. Results demonstrated onset of accelerated decline for fluid (speed, memory) versus crystallized (verbal, clock reading) abilities occurring approximately 10 and 5 years before diagnosis, respectively. Although decline before change points was greater for fluid abilities, acceleration was more pronounced for crystallized abilities after the change points. This suggests that onset and rate of acceleration vary systematically along the fluid-crystallized ability continuum. There is early onset in fluid abilities, but these changes are difficult to detect due to substantial age-related decline. Onset occurred later and acceleration was greater in crystallized abilities, suggesting that those markers may provide more valid identification of cases in later stages of the prodromal phase.
|
|
| 41. |
- Timmers, Maarten, et al.
(författare)
-
Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease.
- 2019
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 79, s. 131-141
-
Tidskriftsartikel (refereegranskat)abstract
- Amyloid β (Aβ) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aβ and tau for cognitive impairment in early AD was examined with cross-sectional analysis, measured by cerebrospinal fluid biomarkers (Aβ1-42, total tau [t-tau], and phosphorylated tau [p-tau181P]), and on cognitive performance by the repeatable battery for assessment of neuropsychological status (RBANS). Participants (n = 246) included cognitively normal (Aβ-), mild cognitively impaired (Aβ-), preclinical AD (Aβ+), and prodromal AD (Aβ+). Overall, cognitive scores (RBANS total scale score) had a moderate negative correlation to t-tau (n = 246; r = -0.434; p < 0.001) and p-tau181P (r = -0.389; p < 0.001). When classified by Aβ status, this correlation to t-tau was applicable only in Aβ+ participants (n = 139; r = -0.451, p < 0.001) but not Aβ- participants (n = 107; r = 0.137, p = 0.16), with identical findings for p-tau. Both tau (p < 0.0001) and interaction of Aβ1-42 with tau (p = 0.006) affected RBANS, but not Aβ1-42 alone. Cognitive/memory performance correlated well with cerebrospinal fluid tau levels across early stages of AD, although the correlation is Aβ dependent.
|
|
| 42. |
- Wallin, Anders, 1950, et al.
(författare)
-
The Gothenburg MCI study: design and distribution of Alzheimer's disease and subcortical vascular disease diagnoses from baseline to 6-year follow-up.
- 2016
-
Ingår i: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 1559-7016. ; 36:1, s. 114-131
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for increased nosological knowledge to enable rational trials in Alzheimer's disease (AD) and related disorders. The ongoing Gothenburg mild cognitive impairment (MCI) study is an attempt to conduct longitudinal in-depth phenotyping of patients with different forms and degrees of cognitive impairment using neuropsychological, neuroimaging, and neurochemical tools. Particular attention is paid to the interplay between AD and subcortical vascular disease, the latter representing a disease entity that may cause or contribute to cognitive impairment with an effect size that may be comparable to AD. Of 664 patients enrolled between 1999 and 2013, 195 were diagnosed with subjective cognitive impairment (SCI), 274 with mild cognitive impairment (MCI), and 195 with dementia, at baseline. Of the 195 (29%) patients with dementia at baseline, 81 (42%) had AD, 27 (14%) SVD, 41 (21%) mixed type dementia (=AD+SVD=MixD), and 46 (23%) other etiologies. After 6 years, 292 SCI/MCI patients were eligible for follow-up. Of these 292, 69 (24%) had converted to dementia (29 (42%) AD, 16 (23%) SVD, 15 (22%) MixD, 9 (13%) other etiologies). The study has shown that it is possible to identify not only AD but also incipient and manifest MixD/SVD in a memory clinic setting. These conditions should be taken into account in clinical trials.Journal of Cerebral Blood Flow & Metabolism advance online publication, 15 July 2015; doi:10.1038/jcbfm.2015.147.
|
|
| 43. |
- Wancata, Johannes, et al.
(författare)
-
Diagnostic criteria influence dementia prevalence.
- 2007
-
Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1064-7481. ; 15:12, s. 1034-45
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to compare the prevalence of dementia using different diagnostic systems, and to investigate the influence of the different diagnostic components (memory impairment, personality changes, definition of other intellectual functions) on the prevalence. METHODS: A general population sample of 1,019 elderly living in Gothenburg, Sweden was investigated by using the Comprehensive Psychopathological Rating Scale as well as specific assessments relevant for dementia diagnoses. Diagnoses were given according to the 9th and 10th version of the International Classification of Diseases (ICD-9, ICD-10) as well as the 3rd revised and 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R, DSM-IV). Further, "historical" criteria for dementia were applied as had been used in older studies. RESULTS: DSM-IV dementia occurred most frequently (9.6%), followed by dementia according to "historical" criteria (7.4%), DSM-III-R (6.3%), ICD-10 (3.1%), and ICD-9 (1.2%). The kappa values for the agreement between the diagnostic systems were between 0.166 and 0.810. The requirement of both long-term and short-term memory impairment in DSM-III-R and personality changes in ICD-10 explained most of the differences. When these requirements were held constant, DSM-III-R, DSM-IV, ICD-10 and "historical" criteria identified predominantly the same persons as demented (kappa: 0.810-1.000). CONCLUSION: Prevalence of dementia varied widely depending on diagnostic classification system used. For DSM-III-R, DSM-IV, ICD-10, and "historical" criteria, the definitions of personality changes and combinations of memory impairment lead to differing prevalence rates, whereas the definitions of other intellectual functions have little impact.
|
|
| 44. |
|
|
| 45. |
- Östling, Svante, 1953, et al.
(författare)
-
Psychotic symptoms and paranoid ideation in a population-based sample of 95-year-olds.
- 2007
-
Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1064-7481. ; 15:12, s. 999-1004
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the 1-year prevalence of psychotic symptoms and schizophrenia in nondemented 95-year-olds, and to examine the relation between psychotic symptoms and other psychiatric symptoms, sensory impairments, and cognitive functioning. PARTICIPANTS: The representative sample was 95-year-olds living in Göteborg, Sweden (N = 338). Individuals with dementia were excluded (N = 175), leaving 163 subjects for this study. DESIGN: This was a cross-sectional population study, including psychiatric and physical examinations, cognitive tests, and interviews with close informants. MEASUREMENTS: Diagnosis of schizophrenia, psychotic symptoms, paranoid ideation and dementia according to Diagnostic and Statistical Manual of Mental Disorders, Third Revision (DSM-III) were measured. Cognitive function was tested with the Mini-Mental State Exam. Other psychiatric symptoms were measured by the Comprehensive Psychopathological Rating Scale. RESULTS: The one-year prevalence of any psychotic symptom was 7.4% (95% confidence interval [CI] 3.8-12.5); including hallucinations 6.7% (95% CI 3.4-11.8) and delusions 0.6% (95% CI 0.0-3.4). Four (2.4%) individuals fulfilled DSM-III-R criteria for schizophrenia. Individuals with psychotic symptoms or paranoid ideation did not differ regarding cognitive functioning compared with individuals without these symptoms. Individuals with hallucinations and paranoid ideation had an increased frequency of previous paranoid personality traits compared with individuals without psychotic symptoms and paranoid ideation. No individuals with psychotic symptoms had a formal thought disorder, incoherence of speech, or flat affect. CONCLUSION: The authors found a high prevalence of psychotic symptoms, paranoid ideation, and schizophrenia in the very old. Most of the symptoms were elucidated by information from key informants, illustrating the importance of including relatives in the evaluation of elderly persons.
|
|
| 46. |
- Östling, Svante, 1953, et al.
(författare)
-
Psychotic Symptoms in a Population-Based Sample of 85-Year-Old Individuals With Dementia.
- 2011
-
Ingår i: Journal of geriatric psychiatry and neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 24:1, s. 3-8
-
Tidskriftsartikel (refereegranskat)abstract
- Psychotic symptoms are common in elderly persons with dementia. These symptoms affect a person's ability to function in daily life and put strain on the caregiver. Most studies focus on psychotic symptoms in clinical samples with Alzheimer disease (AD). Thus, their prevalence and relation with dementia subtype and severity in very old populations is unclear. We assessed a representative sample of 85-year-old individuals living in Gothenburg, Sweden (n = 494) using neuropsychiatric examinations, key informant interviews, and medical record reviews; 147 had dementia. Dementia and its severity were diagnosed in accordance with Diagnostic and Statistical Manual of Mental Disorders (Third Edition, Revision [DSM-III-R]) criteria. Alzheimer disease according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria was diagnosed in 64 persons and vascular dementia (VaD) according to Erkinjuntti criteria was observed in 69. Fourteen had dementia due to other causes. Psychotic symptoms were classified according to DSM-III-R. The prevalence of psychotic symptoms in this very old population was 36% among AD cases compared to 54% in VaD cases (P = .04). Proportions with psychotic symptoms increased with increasing dementia severity in individuals with AD. No such association could be shown in those with VaD. This finding of a high proportion of psychotic symptoms also in individuals with mild severity of VaD should alert health professionals to evaluate dementia in very old patients who present with hallucinations or delusions.
|
|
