| 1. |
- Aksnes, Mari, et al.
(författare)
-
Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium
- 2024
-
Ingår i: COMMUNICATIONS MEDICINE. - 2730-664X. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration.MethodsUsing a 13-plex Discovery Assay (R), we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer's disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium.ResultsHere we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status.ConclusionsSeveral CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored. Delirium is a syndrome in which there are substantial changes in a person's ability to focus, understand, or pay attention to events. Delirium often occurs in response to sudden trauma and is more common in persons with pre-existing cognitive impairment. What happens in the brain during delirium is not well understood. To learn more, we have studied whether markers in the cerebrospinal fluid were altered in people with delirium compared to people without delirium. To understand differences specifically caused by delirium, we included two control groups without acute trauma, one with cognitively healthy participants and one with dementia patients. We found several markers altered in people with delirium, with most of the markers similarly altered in people with cognitive impairment due to dementia. One marker was directly linked to delirium and could potentially shed light on the brain processes that cause the syndrome. Aksnes et al. evaluate the association between matrix metalloproteinases and their tissue inhibitors with delirium. Multivariate regression analyses find that while most associations are explained by acute trauma or pre-existing cognitive impairment, low TIMP-4 could be directly linked to delirium.
|
|
| 2. |
- Fjell, Anders Martin, et al.
(författare)
-
Neuroinflammation and Tau Interact with Amyloid in Predicting Sleep Problems in Aging Independently of Atrophy.
- 2018
-
Ingår i: Cerebral cortex (New York, N.Y. : 1991). - : Oxford University Press (OUP). - 1460-2199 .- 1047-3211. ; 28:8, s. 2775-2785
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 3. |
- Halaas, Nathalie Bodd, et al.
(författare)
-
Neurofilament Light in Serum and Cerebrospinal Fluid of Hip Fracture Patients with Delirium.
- 2018
-
Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 46:5-6, s. 346-357
-
Tidskriftsartikel (refereegranskat)abstract
- Delirium is associated with new-onset dementia, suggesting that delirium pathophysiology involves neuronal injury. Neurofilament light (NFL) is a sensitive biomarker for neuroaxonal injury.NFL was measured in cerebrospinal fluid (CSF) (n = 130), preoperative serum (n = 192), and postoperative serum (n = 280) in hip fracture patients, and in CSF (n = 123) and preoperative serum (n = 134) in cognitively normal older adults undergoing elective surgery. Delirium was diagnosed with the Confusion Assessment Method.Median serum NFL (pg/mL) was elevated in delirium in hip fracture patients (94 vs. 54 pre- and 135 vs. 92 postoperatively, both p < 0.001). Median CSF NFL tended to be higher in hip fracture patients with delirium (1,804 vs. 1,636, p = 0.074). Serum and CSF NFL were positively correlated (ρ = 0.56, p < 0.001).Our findings support an association between neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.
|
|
| 4. |
- Idland, Ane-Victoria, et al.
(författare)
-
CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults.
- 2017
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 49, s. 138-144
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 5. |
- Sajjad, Muhammad Umar, et al.
(författare)
-
Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients.
- 2020
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 73:4, s. 1363-1372
-
Tidskriftsartikel (refereegranskat)abstract
- Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known.The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium.In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer's disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay.Hip fracture patients had significantly higher IL-8 levels (p<0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p=0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p=0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p=0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients.Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.
|
|
| 6. |
- Sala-Llonch, Roser, et al.
(författare)
-
Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition.
- 2017
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 58:3, s. 829-840
-
Tidskriftsartikel (refereegranskat)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.
|
|
