| 1. |
- af Geijerstam, Peder, Doktorand, 1983-, et al.
(author)
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Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden
- 2024
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In: Aging and Disease. - Fort Wortht, TX, United States : Buck Institute for Age Research. - 2152-5250.
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Journal article (peer-reviewed)abstract
- Background: Orthostatic hypotension (OH) is more common in the elderly, and associated with increased mortality. However, its implications in 85-year-olds are not known.Methods: In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH.Results: Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality.Conclusion: OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.
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| 2. |
- Blennow, Kaj, 1958, et al.
(author)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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In: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Journal article (peer-reviewed)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 3. |
- Bränsvik, Vanja, et al.
(author)
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Mortality in patients with behavioural and psychological symptoms of dementia : a registry-based study
- 2021
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In: Aging & Mental Health. - : Routledge. - 1360-7863 .- 1364-6915. ; 25:6, s. 1101-1109
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Journal article (peer-reviewed)abstract
- Objectives: Behavioural and psychological symptoms of dementia (BPSD) are common in patients with dementia. In the elderly population, comorbidities frequently coexist with dementia and mortality in dementia is high. The aim of this study was to investigate the impact of BPSD on mortality in severe dementia.Methods: This study of 11,448 individuals was based on linked information from the Swedish BPSD registry, the National Patient Register and the Cause of Death register. BPSD was assessed with the Neuropsychiatric Inventory (NPI). Cox proportional hazards regressions were performed for survival analysis. To study different degrees of BPSD, data was categorized into groups: no (NPI, 0 points), mild (NPI, 1-3 points on >= 1 item), moderate (NPI, 4-8 points on >= 1 item) and severe (NPI, 9-12 points on >= 1 item) BPSD based on the highest score on any of the BPSD assessed (NPI items).Results: The presence of moderate or severe BPSD was associated with a stepwise increased risk of mortality (hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.08-1.60 and HR 1.74; 95% CI 1.44-2.12, respectively) compared with individuals with no BPSD. In addition, there was an association between total NPI score and mortality (HR 1.01; 95% CI 1.007-1.010). The results remained significant after multivariable adjustment for age, sex, dementia diagnosis, medication, previous myocardial infarction, hip fracture and stroke.Conclusions: The results show a stepwise increase in mortality risk with increased BPSD, highlighting the importance of adequate management of BPSD to reduce mortality in dementia.
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| 4. |
- Gustavsson, Anna Märta, et al.
(author)
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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
- 2020
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In: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 87:1, s. 52-62
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies.METHODS: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991-1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009-2015).RESULTS: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03-1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10-1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77-1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07-3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05-2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87-1.90] for Aβ42 and 1.35 [95% CI = 0.86-2.13] for Aβ42 /p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies.INTERPRETATION: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2019.
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| 5. |
- Hertze, Joakim, et al.
(author)
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Changes in cerebrospinal fluid and blood plasma levels of IGF-II and its binding proteins in Alzheimer's disease : an observational study
- 2014
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In: BMC Neurology. - : BioMed Central. - 1471-2377. ; 14
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Insulin-like Growth Factor (IGF)-related system is implicated in neuroregeneration and cell repair, as well as regulating lifespan. IGF-II, one component of this system, has also been found to affect memory functions in a rat model. In this study we explored changes in the IGF-related system in patients with Alzheimer's disease (AD), including changes in IGF-II levels.METHODS: We measured blood plasma and cerebrospinal fluid (CSF) levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 in 72 healthy controls and 92 patients with AD.RESULTS: We found significantly lower blood plasma levels of IGF-II and IGFBP-3 in patients with AD, compared with controls. The levels of IGF-II and IGFBP-2 were significantly elevated in the CSF from patients with AD. We also found correlations between established CSF biomarkers for AD (tau and P-tau) and components of the IGF system.CONCLUSIONS: CSF and blood plasma levels of IGF-II and some of its binding proteins are changed in patients with AD. Further investigation into this area may unravel important clues to the nature of this disease.
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| 6. |
- Holm, H, et al.
(author)
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Beta-blocker therapy and risk of vascular dementia: A population-based prospective study
- 2020
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In: Vascular pharmacology. - : ELSEVIER SCIENCE INC. - 1537-1891 .- 1879-3649. ; 125
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Journal article (peer-reviewed)abstract
- There are a few studies that report cognitive impairment as a complication of treatment with beta-blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimers and mixed dementia in the prospective population-based Malmo Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimers and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta-blockers and increased risk of vascular dementia.
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| 7. |
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| 8. |
- Nakanishi, Miharu, et al.
(author)
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Time Investment for Program Implementation to Manage Neuropsychiatric Symptoms: An Observational Longitudinal Study in In-Home and Residential Care Settings
- 2020
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In: Journal of Alzheimer's Disease Reports. - : IOS Press. - 2542-4823. ; 4:1, s. 441-453
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Journal article (peer-reviewed)abstract
- Background: There are no studies on how the same psychosocial dementia care program is adapted to both in-home andresidential care settings.Objective: To evaluate the time investment required by professionals to implement a psychosocial dementia care programto manage neuropsychiatric symptoms.Methods: A prospective observational study design was used. The program consisted of 1) a one-day training course,2) three interdisciplinary discussion meetings in five months, and 3) a web-based tool for the continued assessment ofneuropsychiatric symptoms. Care professionals implemented the intervention in in-home (19 in-home care managementagencies and 14 multiple in-home service providers) and residential care settings (19 group homes and eight nursing homes)in Japan from October 2019 to February 2020. The level of neuropsychiatric symptoms for the participants was evaluatedusing the Neuropsychiatric Inventory (NPI: 0–144). The time investment was reported by participating professionals. A totalof 125 persons with dementia were included at baseline.Results: Neuropsychiatric symptoms were significantly decreased at the final follow-up in all types of providers (Cohen’sdrm = 0.44–0.61). The mean (SD) time required for the five-month implementation was 417.9 (219.8) minutes. There wasa mean (SD) decrease of 8.6 (14.0) points in the total NPI score among the 103 persons with completed interventions. The time investment was significantly lower in in-home care management agencies than in group homes, and lower infollow-ups than at baseline assessment.Conclusion: The program implementation may incur a substantial time investment regardless of setting. An additional benefitscheme to reward the time investment would be helpful to encourage implementation until the follow-ups.
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| 9. |
- Nilsson, Erik, et al.
(author)
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Associations of central and brachial blood pressure with cognitive function : a population-based study
- 2016
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In: Journal of Human Hypertension. - : Nature Publishing Group. - 0950-9240 .- 1476-5527. ; 30:2, s. 95-99
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Journal article (peer-reviewed)abstract
- Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.
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| 10. |
- Nägga, Katarina, 1962-
(author)
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Aspects on clinical diagnosis of dementia, with focus on biological markers
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.
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