1. |
- Fjell, Anders Martin, et al.
(author)
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Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy.
- 2018
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In: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 28:8, s. 2775-2785
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Journal article (peer-reviewed)abstract
- Sleep problems relate to brain changes in aging and disease, but the mechanisms are unknown. Studies suggest a relationship between β-amyloid (Aβ) accumulation and sleep, which is likely augmented by interactions with multiple variables. Here, we tested how different cerebrospinal fluid (CSF) biomarkers for brain pathophysiology, brain atrophy, memory function, and depressive symptoms predicted self-reported sleep patterns in 91 cognitively healthy older adults over a 3-year period. The results showed that CSF levels of total- and phosphorylated (P) tau, and YKL-40-a marker of neuroinflammation/astroglial activation-predicted poor sleep in Aβ positive older adults. Interestingly, although brain atrophy was strongly predictive of poor sleep, the relationships between CSF biomarkers and sleep were completely independent of atrophy. A joint analysis showed that unique variance in sleep was explained by P-tau and the P-tau × Aβ interaction, memory function, depressive symptoms, and brain atrophy. The results demonstrate that sleep relates to a range of different pathophysiological processes, underscoring the importance of understanding its impact on neurocognitive changes in aging and people with increased risk of Alzheimer's disease.
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2. |
- Hakamies-Blomqvist, Liisa, et al.
(author)
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Körkortsdiagnostik i allmänläkares dagliga patientarbete med äldre : en jämförelse av svenska och finska allmänläkares aktiviteter, kunskaper och attityder
- 1998
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Reports (other academic/artistic)abstract
- I Sverige och Finland används olika metoder för att identifiera de äldre förare som av medicinska skäl inte borde fortsätta att köra bil. Svenska läkare är skyldiga att rapportera olämpliga förare, men inga medicinska undersökningar krävs för att förlänga ett körkorts giltighet. I Finland upphör körkortet att gälla vid 70 års ålder. De som önskar fortsätta köra bil måste, i samband med ansökan om ett nytt körkort, genomgå en medicinsk kontroll som omfattar det allmänna hälsotillståndet och synförmågan. Syftet med föreliggande undersökning var att jämföra finska och svenska allmänläkares aktiviteter, kunskaper och attityder beträffande åldrande och bilkörning, med avsikten att utvärdera effekterna av de bägge ländernas olika körkortspolicy. Hypotesen var att de finska allmänläkarna, p g a erfarenheten från de obligatoriska hälsokontrollerna, skulle vara bättre informerade och mera aktiva när det gäller att hantera frågan om körlämpligheten med sina äldre patienter än de svenska, som saknar denna typ av erfarenhet. Ett slumpmässigt urval av 3 000 svenska och finska allmänläkare tillfrågades i en postenkät om sina aktiviteter, kunskaper och attityder angående patienter som var aktiva förare och 65 år och däröver. Resultaten visade att den strikta finska policyn för förnyandet av körkortet för äldre förare inte medförde att allmänläkarna var bättre informerade eller mer aktiva när gällde att ta tag i körrelaterade frågor med de äldre patienterna. Skillnaderna var små mellan svenska och finska allmänläkares aktivitetsgrad och kunskapsnivå. De svenska läkarna var emellertid något mer aktiva och visste mer om demens som en riskfaktor. Icke desto mindre hade de finska läkarna en större tilltro till sin förmåga att bedöma körförmågan hos äldre patienter. Deras attityder var också mer restriktiva. Sålunda framkom inget i undersökningen som stödde hypotesen. Det finska systemet ger inte allmänläkarna bättre förutsättningar att hantera frågor om åldrande och bilkörning än de svenska allmänläkarna. Systemet kan till och med motverka sitt eget syfte genom att det hos de finska allmänläkarna skapar en illusorisk tilltro till sin förmåga att bedöma körlämpligheten.
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3. |
- Idland, Ane-Victoria, et al.
(author)
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CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults.
- 2017
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In: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 49, s. 138-144
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) neurofilament light (NFL) is a marker of axonal degeneration. We tested whether CSF NFL levels predict hippocampal atrophy rate in cognitively healthy older adults independently of the established CSF Alzheimer's disease (AD) biomarkers, β-amyloid 1-42, and phosphorylated tau (P-tau). We included 144 participants in a 2-year longitudinal study with baseline CSF measures and2 magnetic resonance images. Eighty-eight participants had full data available. A subgroup of 36participants with very low AD risk was also studied. NFL predicted hippocampal atrophy rate independently of age, β-amyloid 1-42, and P-tau. Including NFL, P-tau, and age in the same model, higher NFL and lower P-tau predicted higher hippocampal atrophy (R(2)= 0.20, NFL: β=-0.34; p= 0.003; P-tau: β= 0.27; p= 0.009). The results were upheld in the participants with very low AD risk. NFL predicted neurodegeneration in older adults with very low AD probability. We suggest that factors previously shown to be important for brain degeneration in mild cognitive impairment may also impact changes innormal aging, demonstrating that NFL is likely to indicate AD-independent, age-expected neurodegeneration.
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4. |
- Idland, Ane Victoria, et al.
(author)
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Preclinical amyloid-β and axonal degeneration pathology in delirium
- 2016
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 55:1, s. 371-379
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Journal article (peer-reviewed)abstract
- Background: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. Objective: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. Methods: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ42, T-tau, and P-tau were analyzed. Results: In patients without dementia, we found lower CSF Aβ42 levels (median, 310ng/L versus 489ng/L, p=0.006), higher T-tau levels (median, 505ng/L versus 351ng/L, p=0.02), but no change in P-tau in patients who developed delirium (n=16) compared to those who remained lucid (n=49). Delirious patients also had lower ratios of Aβ42 to T-tau (p<0.001) and P-tau (p=0.001) relative to those without delirium. CSF Aβ42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n=54) and without delirium (n=10). Conclusion: The reduction in CSF Aβ42, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.
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6. |
- Sala-Llonch, Roser, et al.
(author)
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Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition.
- 2017
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 58:3, s. 829-840
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Journal article (peer-reviewed)abstract
- Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer's disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiology. Whether and how Aβ and YKL-40 affect brain and cognitive changes in cognitively healthy older adults is still unknown. We studied 89 participants (mean age: 73.1 years) with cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments from two time-points separated by two years. We tested how baseline levels of Aβ42 and YKL-40 correlated with changes in cortical thickness and cognition. Thickness change correlated with Aβ42 only in Aβ42+ participants (<600 pg/mL, n=27) in the left motor and premotor cortices. Aβ42 was unrelated to cognitive change. Increased YKL-40 was associated with less preservation of scores on the animal naming test in the total sample (r=-0.28, p=0.012) and less preservation of a score reflecting global cognitive function for Aβ42+ participants (r=-0.58, p=0.004). Our results suggest a role for inflammation in brain atrophy and cognitive changes in cognitively normal older adults, which partly depended on Aβ accumulation.
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7. |
- Styrkarsdottir, Unnur, et al.
(author)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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Journal article (peer-reviewed)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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8. |
- Vlachos, Georgios, et al.
(author)
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Cognitive and emotional symptoms in patients with first-ever mild stroke : The syndrome of hidden impairments
- 2021
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In: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 53:1
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the prevalence of cognitive and emotional impairments one year after first-ever mild stroke in younger patients.Design: Prospective, observational, cohort study.Subjects: A consecutive sample of 117 previously cognitively healthy patients aged 18-70 years with mild stroke (National Institutes of Health Stroke Scale score <= 3) were included in 2 hospitals in Norway during a 2-year period.Methods: At 12-month follow-up, patients were assessed using validated instruments for essential cognitive domains, fatigue, depression, anxiety, apathy and pathological laughter and crying.Results: In total, 78 patients (67%) had difficulty with one or a combination of the cognitive domains psychomotor speed, attention, executive and visuospatial function, and memory. Furthermore, 50 patients (43%) had impairment in either one or a combination of the emotional measures for anxiety, depressive symptoms, fatigue, apathy or emotional lability. A total of 32 patients (28%) had both cognitive and emotional impairments. Only 21 patients (18%) scored within the reference range in all the cognitive and emotional tools.Conclusion: Hidden impairments are common after first-ever mild stroke in younger patients. Stroke physicians should screen for hidden impairments using appropriate tools.
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9. |
- Vlachos, Georgios, et al.
(author)
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Factors Determining Not Returning to Full-Time Work 12 Months After Mild Ischemic Stroke
- 2023
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In: Archives of Rehabilitation Research and Clinical Translation. - : Elsevier. - 2590-1095. ; 5:1
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate prevalence and factors determining not returning to full-time work 1 year after first-ever mild ischemic stroke. DESIGN: Prospective, observational cohort study with 12-month follow-up.SETTING: Stroke units and outpatient clinics at 2 Norwegian hospitals. PARTICIPANTS: We included 84 (N=84) full-time working, cognitively healthy patients aged 70 years or younger who suffered an acute first-ever mild ischemic stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score ≤3 points. INTERVENTIONS: Not applicable.MAIN OUTCOME MEASURES: Vascular risk factors, sociodemographic factors, stroke localization, and etiology were recorded at inclusion. Cognitive impairment, anxiety, depression, fatigue, and apathy 12 months after stroke were assessed with validated instruments. Logistic regression analyses were performed to find correlates of not returning to full-time employment.RESULTS: Of 78 patients assessed 1 year after stroke, 63 (81%) had returned to work, 47 (60%) to full-time employment status. Modified Rankin scale score >1 (adjusted odds ratio, 12.44 [95% confidence interval, 2.37-65.43], P=.003) at follow-up was significantly associated, and diabetes (adjusted odds ratio, 10.56 [95% confidence interval, 0.98-113.47], P=.052) was borderline significantly associated with not returning to full-time work. Female sex, NIHSS at discharge, anxiety per point on the anxiety scale, depression per point on the depression scale, and fatigue per point on the fatigue scale were significantly associated with not returning to full-time work after 1 year, but these associations were only seen in the unadjusted models.CONCLUSIONS: Low functional level that persists 12 months after stroke is related to not returning to full-time work. Patients with diabetes mellitus, female patients, and patients with a higher score on fatigue, anxiety, and depression scales may also be at risk of not returning to full-time work post stroke. Working patients should be followed up with a particular focus on factors determining participation in work and social life.
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10. |
- Vlachos, Georgios, et al.
(author)
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Predictors of cognitive and emotional symptoms 12 months after first-ever mild stroke
- 2023
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In: Neuropsychological rehabilitation (Print). - : Routledge. - 0960-2011 .- 1464-0694. ; 33:4, s. 662-679
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Journal article (peer-reviewed)abstract
- Even mild strokes may affect the patients' everyday life by impairing cognitive and emotional functions. Our aim was to study predictors of such impairments one year after first-ever mild stroke. We included cognitively healthy patients ≤ 70 years with acute mild stroke. Vascular risk factors, sociodemographic factors and stroke classifications were recorded. At one-year post-stroke, different domains related to cognitive and emotional function were assessed with validated instruments. Logistic regression analyses were performed to identify predictors of cognitive and emotional outcome. Of 117 patient assessed at follow-up, only 21 patients (18%) scored within the reference range on all cognitive and emotional assessments. Younger age, multiple infarcts, and being outside working life at stroke onset were independent predictors of cognitive impairments (psychomotor speed, attention, executive and visuospatial function, memory). Female gender and a higher National Institutes of Health Stroke Scale (NIHSS) score at discharge were significantly associated with emotional impairments (anxiety, depressive symptoms, fatigue, apathy, emotional lability) after one year, but these associations were only seen in the unadjusted models. In conclusion, patients in working age may profit from a follow-up during the post-stroke period, with extra focus on cognitive and emotional functions.
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