scholarly journals No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - a seven-year follow-up study

2020 ◽  
Author(s):  
Guri Hagberg ◽  
Hege Ihle-Hansen ◽  
Brynjar Fure ◽  
Bente Thommessen ◽  
Håkon Ihle-Hansen ◽  
...  

Abstract Background: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after seven years correlates with amyloid-β peptide (Aβ₄₂) levels in cerebrospinal fluid (CSF) at one year, and with measures of neurodegeneration and cognition at seven years post-stroke. Methods: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At seven years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ₄₂ levels were assessed using linear regression. Results: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from one year. Thirteen out of 26 patients were diagnosed with CI seven years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ₄₂ levels at one year, MTA grade, GCA scale, MMSE score or TMT-A at seven years did not correlate with 18F-Flut-PET SUVr in this cohort.Conclusions: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration seven years post-stroke.Trial registration: Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

2020 ◽  
Author(s):  
Guri Hagberg ◽  
Hege Ihle-Hansen ◽  
Brynjar Fure ◽  
Bente Thommessen ◽  
Håkon Ihle-Hansen ◽  
...  

Abstract Background: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in 7-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after seven years correlates with amyloid-β peptide (Aβ₄₂) levels in cerebrospinal fluid (CSF) at one year, and with measures of neurodegeneration and cognition at seven years post-stroke. Methods: 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At seven years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ₄₂ levels were assessed using linear regression. Results: In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from one year. Thirteen out of 26 patients were diagnosed with CI seven years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ₄₂ levels at one year, MTA grade, GCA scale, MMSE score or TMT-A at seven years did not correlate with 18F-Flut-PET SUVr in this cohort.Conclusions: Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore amyloid pathology may not be a key mediator of neurodegeneration seven years post-stroke.Trial registration: Clinicaltrials.gov (NCT00506818)


2020 ◽  
Author(s):  
Guri Hagberg ◽  
Hege Ihle-Hansen ◽  
Brynjar Fure ◽  
Bente Thommessen ◽  
Håkon Ihle-Hansen ◽  
...  

Abstract Background Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol ( 18 F-Flut) positron emission tomography (PET), is common in 7-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18 F-Flut-PET uptake after seven years correlates with amyloid-β peptide (Aβ 42 ) levels in cerebrospinal fluid (CSF) at one year, and with measures of neurodegeneration and cognition at seven years post-stroke. Methods 208 patients with first-ever stroke or TIA without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or none. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At seven years, patients were offered 18 F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18 F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ 42 levels were assessed using linear regression. Results In all, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from one year. Thirteen out of 26 patients were diagnosed with CI seven years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ 42 levels at one year, MTA grade, GCA scale, MMSE score or TMT-A at seven years did not correlate with 18 F-Flut-PET SUVr in this cohort. Conclusions Amyloid binding were not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed amyloid did not correlate with other measures related to neurodegeneration and cognition. Therefore amyloid pathology may not be a key mediator of neurodegeneration seven years post-stroke.


2019 ◽  
Author(s):  
Guri Hagberg ◽  
Hege Ihle-Hansen ◽  
Brynjar Fure ◽  
Bente Thommessen ◽  
Håkon Ihle-Hansen ◽  
...  

Abstract Background: Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in 7-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after seven years correlates with amyloid-β peptide (Aβ₄₂) levels in cerebrospinal fluid (CSF) at one year, and with measures of neurodegeneration and cognition at seven years post-stroke. Methods: 208 patients with first-ever stroke or TIA without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or none. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At seven years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ₄₂ levels were assessed using linear regression. Results: In all, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from one year. Thirteen out of 26 patients were diagnosed with CI seven years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ₄₂ levels at one year, MTA grade, GCA scale, MMSE score or TMT-A at seven years did not correlate with 18F-Flut-PET SUVr in this cohort.Conclusions: Amyloid binding were not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed amyloid did not correlate with other measures related to neurodegeneration and cognition. Therefore amyloid pathology may not be a key mediator of neurodegeneration seven years post-stroke.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Stephen Makin ◽  
Martin Dennis ◽  
Joanna M Wardlaw

Background: Up to one third of patients with a clinically apparent mild stroke and no other apparent cause of their symptoms have a normal MRI. We examined disability, recurrent stroke, and cognitive impairment at one year compared to patient with an MRI-DWI lesion. Methods: We recruited consecutive patients with a non-disabling ischaemic stroke, and performed clinical assessment and MRI (with DWI) . An expert panel reviewed all cases, we included patients with a final diagnosis of stroke and excluded patients with another diagnosis. At one year post stroke we recorded modified Rankin scale (mRs), stroke and TIA recurrence, Addenbrookes Cognitive Assessment Revised (ACE-R) and the Beck Depression index (BDI) and performed another MRI. Non-attenders were assessed by telephone or post. We defined cognitive impairment as ACE-R of <88, and depression as a BDI of >9. Results: Almost one third (75/264) (median NIHSS=2) of patients had a no relevant lesion on MRI DWI. There was no difference in age, sex, symptoms, or risk factors in patients with and without a lesion, 197 had MRI at 1 year (all had clinical follow-up). Of 75 with no lesion, 41% were mRs ≥2, 13% had recurrent stroke or TIA, 36% were cognitively impaired and 46% had depression. This was not significantly different from the patients with a lesion. Of the 197 who had a follow-up MRI 50 patients with no initial lesion had follow-up MRI and one had a new lesion, (versus 20/147 patients with a lesion) (p=0.016). Conclusions: Patients with a clinical stroke and no other obvious cause for their symptoms are clinically indistinguishable from patients with the same NIHSS who have a lesion on DWI-MRI, in terms of recurrence, disability, or cognitive impairment. Suggesting that these patients have had a stroke that does not appear on MRI. The presence of an initial lesion increases the liklihood of a lesion on 1 year MRI, however without a difference in clinical stroke this is of doubtful significance.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shilpa Tyagi ◽  
Gerald Choon-Huat Koh ◽  
Nan Luo ◽  
Kelvin Bryan Tan ◽  
Helen Hoenig ◽  
...  

Abstract Background Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. Method Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0–3 months (early) and 4–12 months (late) post-stroke. Results For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. Conclusion We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.


2019 ◽  
Author(s):  
Rewadee Jenraumjit ◽  
Surarong Chinwong ◽  
Dujrudee Chinwong ◽  
Tipaporn Kanjanarach ◽  
Thanat Kshetradat ◽  
...  

Abstract Objective Age-associated decline in central cholinergic activity makes older adults susceptible to harmful effects of anticholinergics (ACs). Evidence exists of an association between effects of AC medications on cognition. This retrospective cohort study examines how ACs affect cognition among older adults with Alzheimer’s disease (AD) who received acetylcholine esterase inhibitors (AChEIs) over the course of 12 months. Results A total of 133 (80% women, mean age 78.38 years, SD 7.4) were recruited. No difference in sex, age and comorbid diseases was observed between participants who took ACs, Benzodiazepines (BZDs) and AChEIs. The most common prescribed ACs was quetiapine, being used for behavioral and psychological symptoms (BPSD). Multilevel analysis showed that the change of mental state examination scores were significantly predicted in the group using ACs (t (169), -2.52, p = .020) but not with the groups using BZD (t (162), 0.84, p = .440). Evidence showed that older adults with Alzheimer’s disease and exposed to ACs exhibited lower global cognitive scores than those without AC exposure. Using ACs could be a trade-off between controlling BPSD and aggravating cognitive impairment. Highlighting the awareness of the potential anticholinergic effect is important and may be the best policy.


2012 ◽  
Vol 6 (3) ◽  
pp. 152-157 ◽  
Author(s):  
Luisa Terroni ◽  
Matildes F.M. Sobreiro ◽  
Adriana B. Conforto ◽  
Carla C. Adda ◽  
Valeri D. Guajardo ◽  
...  

ABSTRACT The relationship between depression and cognitive impairment, frequent after stroke, is complex and has not been sufficiently elucidated. Objective: To review the relationship between post-stroke depression and cognitive impairment. Methods: We performed a PubMed database search spanning the last ten years, using the terms post-stroke depression, cognitive dysfunction, cognitive impairment and neuropsychological tests. Our target studies were original quantitative studies that investigated the relationship between post-stroke depression (PSD) and cognitive impairment in stroke patients. Articles published in English, Spanish, Italian and Portuguese were considered. Selection criteria were the use of neuropsychological tests to assess cognitive function, and of either instruments to diagnose major depression, or scales to assess depressive symptoms, within the first three months after stroke. Results: Six original quantitative studies fulfilled the criteria. The prevalence of PSD within the first three months after stroke ranged from 22% to 31%. Incidence ranged from 25% to 27% and was evaluated in only two studies. PSD was associated with increased cognitive impairment. Cognitive impairment was reported in 35.2% to 87% of the patients. Post-stroke cognitive deficits were reported mostly in executive function, memory, language, and speed of processing. Conclusion: Executive dysfunction and depression occur in stroke survivors, are frequently coexistent, and also associated with worse stroke prognosis. Healthcare professionals need to address and provide adequate treatment for depression and executive dysfunctions in stroke patients early in the first three months after stroke. Future studies should evaluate the efficacy of programs evaluating the early detection and treatment of PSD and executive dysfunction in stroke survivors.


2020 ◽  
Vol 77 (2) ◽  
pp. 689-699
Author(s):  
Maurizio Gallucci ◽  
Anna Paola Mazzarolo ◽  
Lucia Focella ◽  
Cinzia Piovesan ◽  
Manuela Mazzetto ◽  
...  

Background: Frailty is a condition of increased vulnerability to exogenous and endogenous stressors, which is correlated with aging, functional decline, institutionalization, hospitalization, and mortality. Given the multifaceted nature of frailty, programs aimed at its prevention are recommended to act on multiple domains. Objective: The present intervention program aimed at assessing the effects of combined physical and cognitive training in older people with mild cognitive impairment (MCI) and at investigating how their frailty status changed over one year of follow-up. Methods: Two-hundred and seven participants were recruited among outpatients of the Cognitive Impairment Center who agreed to receive a comprehensive assessment. Forty-six participants, who joined a structured program of physical activity and group readings for a period of one year, were defined as active. The remaining 161, who decided not to engage in those activities, were considered controls. In both groups, frailty status was assessed at baseline and over one year of follow-up. Results: Control participants showed twice the risk of becoming frail at 12 months compared with those in the active group. Participants in the active group had more than three times the probability of improving their frailty status compared with the control group from T0 to T12. Age and NPI scores were significantly associated with worsening frailty status. When analyses were restricted to participants who were robust at baseline, the frailty status varied significantly between groups over time. Conclusion: Findings of the present study confirm the beneficial effects of physical activity and reading to prevent frailty in older people with MCI.


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