| 21. |
- Benussi, Alberto, et al.
(författare)
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Prodromal frontotemporal dementia: clinical features and predictors of progression.
- 2021
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The prodromal phase of frontotemporal dementia (FTD) is still not well characterized, and conversion rates to dementia and predictors of progression at 1-year follow-up are currently unknown.In this retrospective study, disease severity was assessed using the global CDR plus NACC FTLD. Prodromal FTD was defined to reflect mild cognitive or behavioural impairment with relatively preserved functional independence (global CDR plus NACC = 0.5) as well as mild, moderate and severe dementia (classified as global CDR plus NACC = 1, 2, 3, respectively). Disease progression at 1-year follow-up and serum NfL measurements were acquired in a subgroup of patients.Of 563 participants, 138 were classified as prodromal FTD, 130 as mild, 175 as moderate and 120 as severe FTD. In the prodromal and mild phases, we observed an early increase in serum NfL levels followed by behavioural disturbances and deficits in executive functions. Negative symptoms, such as apathy, inflexibility and loss of insight, predominated in the prodromal phase. Serum NfL levels were significantly increased in the prodromal phase compared with healthy controls (average difference 14.5, 95% CI 2.9 to 26.1 pg/mL), but lower than in patients with mild FTD (average difference -15.5, 95% CI -28.4 to -2.7 pg/mL). At 1-year follow-up, 51.2% of patients in the prodromal phase had converted to dementia. Serum NfL measurements at baseline were the strongest predictors of disease progression at 1-year follow-up (OR 1.07, 95% CI 1.03 to 1.11, p < 0.001).Prodromal FTD is a mutable stage with high rate of progression to fully symptomatic disease at 1-year follow-up. High serum NfL levels may support prodromal FTD diagnosis and represent a helpful marker to assess disease progression.
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| 22. |
- Bernick, Charles, et al.
(författare)
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Blood biomarkers and neurodegeneration in individuals exposed to repetitive head impacts.
- 2023
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Ingår i: Alzheimer's research & therapy. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown if fluid biomarkers reflective of brain pathologies are useful in detecting and following a neurodegenerative process in individuals exposed to repetitive head impacts. This study explores the relationship between blood biomarkers and longitudinal change in cognitive function and regional brain volumes in a cohort of professional fighters.Participants are drawn from a convenience sample of active and retired professional boxers and Mixed Martial Arts fighters and a control group with no prior exposure to head impacts. 3 T MRI brain imaging, plasma samples, and computerized cognitive testing were obtained at baseline and, for a subset, annually. MRI regional volumes were extracted, along with plasma levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), p-tau231, and N-terminal tau (NTA). Statistical analyses were performed to assess the relationship between plasma levels and regional brain volumes and cognitive performance at baseline and longitudinally.One hundred forty active boxers (mean age: 31 with standard deviation (SD) of 8), 211 active MMA (mean age of 30 with SD of 5), 69 retired boxers (mean age 49 with SD of 9), and 52 control participants (mean age 36 with SD of 12) were included in the analyses. Baseline GFAP levels were highest in the retired boxers (retired boxers v. active MMA: p = 0.0191), whereas active boxers had higher levels of NfL (active boxers v. MMA: p = 0.047). GFAP showed an increase longitudinally in retired boxers that was associated with decreasing volumes of multiple cortical and subcortical structures (e.g., hippocampus: B = - 1.25, 95% CI, - 1.65 to - 0.85) and increase in lateral ventricle size (B = 1.75, 95% CI, 1.46 to 2.04). Furthermore, performance on cognitive domains including memory, processing speed, psychomotor speed, and reaction time declined over time with increasing GFAP (e.g., processing speed: B = - 0.04, 95% CI, - 0.07 to - 0.02; reaction time: B = 0.52, 95% CI, 0.28 to 0.76). Among active fighters, increasing levels of GFAP were correlated with lower thalamic (B = - 1.42, 95% CI, - 2.34 to -0.49) and corpus callosum volumes, along with worsening scores on psychomotor speed (B = 0.14, 95% CI, 0.01 to 0.27).Longitudinal plasma GFAP levels may have a role in identifying individuals exposed to repetitive head impacts who are at risk of showing progressive regional atrophy and cognitive decline.
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| 23. |
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| 24. |
- Biel, D., et al.
(författare)
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Combining tau-PET and fMRI meta-analyses for patient-centered prediction of cognitive decline in Alzheimer's disease
- 2022
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Tau-PET is a prognostic marker for cognitive decline in Alzheimer's disease, and the heterogeneity of tau-PET patterns matches cognitive symptom heterogeneity. Thus, tau-PET may allow precision-medicine prediction of individual tau-related cognitive trajectories, which can be important for determining patient-specific cognitive endpoints in clinical trials. Here, we aimed to examine whether tau-PET in cognitive-domain-specific brain regions, identified via fMRI meta-analyses, allows the prediction of domain-specific cognitive decline. Further, we aimed to determine whether tau-PET-informed personalized cognitive composites capture patient-specific cognitive trajectories more sensitively than conventional cognitive measures. Methods We included Alzheimer's Disease Neuroimaging Initiative (ADNI) participants classified as controls (i.e., amyloid-negative, cognitively normal, n = 121) or Alzheimer's disease-spectrum (i.e., amyloid-positive, cognitively normal to dementia, n = 140), plus 111 AVID-1451-A05 participants for independent validation (controls/Alzheimer's disease-spectrum=46/65). All participants underwent baseline F-18-flortaucipir tau-PET, amyloid-PET, and longitudinal cognitive testing to assess annual cognitive changes (i.e., episodic memory, language, executive functioning, visuospatial). Cognitive changes were calculated using linear mixed models. Independent meta-analytical task-fMRI activation maps for each included cognitive domain were obtained from the Neurosynth database and applied to tau-PET to determine tau-PET signal in cognitive-domain-specific brain regions. In bootstrapped linear regression, we assessed the strength of the relationship (i.e., partial R-2) between cognitive-domain-specific tau-PET vs. global or temporal-lobe tau-PET and cognitive changes. Further, we used tau-PET-based prediction of domain-specific decline to compose personalized cognitive composites that were tailored to capture patient-specific cognitive decline. Results In both amyloid-positive cohorts (ADNI [age = 75.99 +/- 7.69] and A05 [age = 74.03 +/- 9.03]), cognitive-domain-specific tau-PET outperformed global and temporal-lobe tau-PET for predicting future cognitive decline in episodic memory, language, executive functioning, and visuospatial abilities. Further, a tau-PET-informed personalized cognitive composite across cognitive domains enhanced the sensitivity to assess cognitive decline in amyloid-positive subjects, yielding lower sample sizes required for detecting simulated intervention effects compared to conventional cognitive endpoints (i.e., memory composite, global cognitive composite). However, the latter effect was less strong in A05 compared to the ADNI cohort. Conclusion Combining tau-PET with task-fMRI-derived maps of major cognitive domains facilitates the prediction of domain-specific cognitive decline. This approach may help to increase the sensitivity to detect Alzheimer's disease-related cognitive decline and to determine personalized cognitive endpoints in clinical trials.
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| 25. |
- Blennow, Kaj, 1958, et al.
(författare)
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Is it time for biomarker-based diagnostic criteria for prodromal Alzheimer's disease?
- 2010
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 2:2
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Forskningsöversikt (refereegranskat)abstract
- ABSTRACT: Drug candidates targeting amyloid-beta (Abeta) pathology in Alzheimer's disease are in different phases of clinical trials. These treatments will probably be most effective in the earlier stages of the disease, before neurodegeneration is too severe, but at the same time symptoms are vague and the clinical diagnosis is difficult. Recent research advances have resulted in promising biomarkers, including cerebrospinal fluid analyses for tau and Abeta, magnetic resonance imaging measurement of atrophy, and positron emission tomography imaging of glucose metabolism and Abeta pathology, which allow identification of prodromal Alzheimer's disease. More details are needed, however, on how these biomarkers can be standardized, to allow a general implementation in the clinical routine diagnostic work-up of patients with cognitive disturbances.
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| 26. |
- Bloniecki, Victor, et al.
(författare)
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Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.METHODS: A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer's disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1-42, Ng, NFL, and GAP-43.RESULTS: No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.CONCLUSION: Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.
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| 27. |
- Borland, Emma, et al.
(författare)
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The age-related effect on cognitive performance in cognitively healthy elderly is mainly caused by underlying AD pathology or cerebrovascular lesions : implications for cutoffs regarding cognitive impairment
- 2020
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Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As research in treatments for neurocognitive diseases progresses, there is an increasing need to identify cognitive decline in the earliest stages of disease for initiation of treatment in addition to determining the efficacy of treatment. For early identification, accurate cognitive tests cutoff values for cognitive impairment are essential. METHODS: We conducted a study on 297 cognitively healthy elderly people from the BioFINDER study and created subgroups excluding people with signs of underlying neuropathology, i.e., abnormal cerebrospinal fluid [CSF] β-amyloid or phosphorylated tau, CSF neurofilament light (neurodegeneration), or cerebrovascular pathology. We compared cognitive test results between groups and examined the age effect on cognitive test results. RESULTS: In our subcohort without any measurable pathology (n = 120), participants achieved better test scores and significantly stricter cutoffs for cognitive impairment for almost all the examined tests. The age effect in this subcohort disappeared for all cognitive tests, apart from some attention/executive tests, predominantly explained by the exclusion of cerebrovascular pathology. CONCLUSION: Our study illustrates a new approach to establish normative data that could be useful to identify earlier cognitive changes in preclinical dementias. Future studies need to investigate if there is a genuine effect of healthy aging on cognitive tests or if this age effect is a proxy for higher prevalence of preclinical neurodegenerative diseases.
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| 28. |
- Bos, Isabelle, et al.
(författare)
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Cerebrovascular and amyloid pathology in predementia stages : the relationship with neurodegeneration and cognitive decline
- 2017
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics.RESULTS: MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline.CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.
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| 29. |
- Bos, Isabelle, et al.
(författare)
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Correction to : Cerebrovascular and amyloid pathology in predementia stages
- 2018
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 10:56
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Tidskriftsartikel (refereegranskat)abstract
- Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables 1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables.
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| 30. |
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