| 31. |
- Gonzalez, Maria Camila, et al.
(författare)
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Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
- 2023
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Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
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| 32. |
- Gonzalez-Ortiz, Fernando, 1990, et al.
(författare)
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Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer's disease.
- 2024
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Ingår i: Nature communications. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer's disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n=1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ ("A") and neurodegeneration ("N") abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
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| 33. |
- Gurholt, Tiril P., et al.
(författare)
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Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study
- 2024
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Ingår i: Brain Communications. - : OXFORD UNIV PRESS. - 2632-1297. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance. We included 33 709 UK Biobank participants (54.2% female; age range 44-82 years) with structural and diffusion magnetic resonance imaging, thigh muscle fat infiltration (n = 30 561) from whole-body magnetic resonance imaging (muscle quality indicator) and general cognitive performance as indicated by the first principal component of a principal component analysis across multiple cognitive tests (n = 22 530). Of these, 1703 participants qualified for probable sarcopenia based on low handgrip strength, and we assigned the remaining 32 006 participants to the non-sarcopenia group. We used multiple linear regression to test how sarcopenic traits (probable sarcopenia versus non-sarcopenia and percentage of thigh muscle fat infiltration) relate to cognitive performance and brain structure (cortical thickness and area, white matter fractional anisotropy and deep and lower brain volumes). Next, we used structural equation modelling to test whether brain structure mediated the association between sarcopenic and cognitive traits. We adjusted all statistical analyses for confounders. We show that sarcopenic traits (probable sarcopenia versus non-sarcopenia and muscle fat infiltration) are significantly associated with lower cognitive performance and various brain magnetic resonance imaging measures. In probable sarcopenia, for the included brain regions, we observed widespread significant lower white matter fractional anisotropy (77.1% of tracts), predominantly lower regional brain volumes (61.3% of volumes) and thinner cortical thickness (37.9% of parcellations), with |r| effect sizes in (0.02, 0.06) and P-values in (0.0002, 4.2e(-29)). In contrast, we observed significant associations between higher muscle fat infiltration and widespread thinner cortical thickness (76.5% of parcellations), lower white matter fractional anisotropy (62.5% of tracts) and predominantly lower brain volumes (35.5% of volumes), with |r| effect sizes in (0.02, 0.07) and P-values in (0.0002, 1.9e(-31)). The regions showing the most significant effect sizes across the cortex, white matter and volumes were of the sensorimotor system. Structural equation modelling analysis revealed that sensorimotor brain regions mediate the link between sarcopenic and cognitive traits [probable sarcopenia: P-values in (0.0001, 1.0e-11); muscle fat infiltration: P-values in (7.7e(-05), 1.7e(-12))]. Our findings show significant associations between sarcopenic traits, brain structure and cognitive performance in a middle-aged and older adult population. Mediation analyses suggest that regional brain structure mediates the association between sarcopenic and cognitive traits, with potential implications for dementia development and prevention.
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| 34. |
- Holmgren, Simon, et al.
(författare)
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Neuropsychiatric symptoms in dementia : a role for neuroinflammation?
- 2014
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Ingår i: Brain Research Bulletin. - : Elsevier. - 0361-9230 .- 1873-2747. ; 108, s. 88-93
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Tidskriftsartikel (refereegranskat)abstract
- Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.
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| 35. |
- Holmgren, Simon, et al.
(författare)
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Neuropsychiatric Symptoms in Dementia : Considering a Clinical Role for Electroencephalography
- 2022
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Ingår i: The Journal of Neuropsychiatry and Clinical Neurosciences. - : American Psychiatric Association Publishing, Inc.. - 0895-0172 .- 1545-7222. ; 34:3, s. 214-223
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Degenerative dementia is characterized by progressive cognitive decline and neuropsychiatric symptoms. People with Alzheimer's disease (AD), the most common cause of dementia, show synaptic loss and disruption of functional brain networks along with neuritic plaques and neurofibrillary tangles. Electroencephalography (EEG) directly reflects synaptic activity, and among patients with AD it is associated with slowing of background activity. The purpose of this study was to identify associations between neuropsychiatric symptoms and EEG in patients with dementia and to determine whether EEG parameters could be used for clinical assessment of pharmacological treatment of neuropsychiatric symptoms in dementia (NPSD) with galantamine or risperidone.METHODS: Seventy-two patients with EEG recordings and a score ≥10 on the Neuropsychiatric Inventory (NPI) were included. Clinical assessments included administration of the NPI, the Mini-Mental State Examination (MMSE), and the Cohen-Mansfield Agitation Inventory (CMAI). Patients underwent EEG examinations at baseline and after 12 weeks of treatment with galantamine or risperidone. EEG frequency analysis was performed. Correlations between EEG and assessment scale scores were statistically examined, as were EEG changes from baseline to the week 12 visit and the relationship with NPI, CMAI, and MMSE scores.RESULTS: Significant correlations were found between NPI agitation and delta EEG frequencies at baseline and week 12. No other consistent and significant relationships were observed between NPSD and EEG at baseline, after NPSD treatment, or in the change in EEG from baseline to follow-up.CONCLUSIONS: The limited informative findings in this study suggest that there exists a complex relationship between NPSD and EEG; hence, it is difficult to evaluate and use EEG for clinical assessment of pharmacological NPSD treatment.
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| 36. |
- Huber, Maria, et al.
(författare)
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Metabolic correlates of dopaminergic loss in dementia with lewy bodies
- 2020
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Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
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Tidskriftsartikel (refereegranskat)abstract
- Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 37. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 38. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 39. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 40. |
- Jones, Emma L., et al.
(författare)
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A Pilot Study Examining Associations between DYRK1A and alpha-Synuclein Dementias
- 2012
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Ingår i: Neurodegenerative Diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 10:1-4, s. 229-231
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Tidskriftsartikel (refereegranskat)abstract
- Background: DYRK1A is a kinase targeting several proteins associated with the pathology of dementias, including alpha-synuclein and amyloid precursor protein. It is not clear if DYRK1A genetics are associated with neurodegenerative conditions. Objective: To determine if DYRK1A also has a genetic association with alpha-synuclein dementias such as dementia with Lewy bodies and Parkinson's disease dementia. Methods: DNA samples from prospectively followed cohorts of control and dementia individuals were genotyped for the DYRK1A rs8126696 polymorphism. Results: The rs8126696 polymorphism altered the risk of developing an alpha-synuclein-associated dementia. Conclusion: DYRK1A could prove to be an important therapeutic target as it interacts with several proteins associated with the development of pathology in dementia. Copyright (C) 2012 S. Karger AG, Basel
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