9 research outputs found
Preanalytical stability of plasma biomarkers for Alzheimer's disease pathology
Introduction
Plasma tests have demonstrated high diagnostic accuracy for identifying Alzheimer's disease pathology. To facilitate the transition to clinical utility, we assessed whether plasma storage duration and temperature affect the biomarker concentrations.
Methods
Plasma samples from 13 participants were stored at +4°C and +18°C. Concentrations of six biomarkers were measured after 2, 4, 6, 8, 10, and 24 h by single molecule array assays.
Results
Phosphorylated tau 181 (p-tau181), phosphorylated tau 231 (p-tau231), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) concentrations were unchanged both when stored at +4°C and +18°C. Amyloid-β 40 (Aβ40) and amyloid-β 42 (Aβ42) concentrations were stable for 24 h at +4°C but declined when stored at +18°C for longer than 6 h. This decline did not affect the Aβ42/Aβ40 ratio.
Discussion
Plasma samples can be stored for 24 h at +4°C or +18°C and result in valid assay results for p-tau181, p-tau231, Aβ42/Aβ40 ratio, GFAP, and NfL.publishedVersio
The individual course of neuropsychiatric symptoms in people with Alzheimerâs and Lewy body dementia: 12-year longitudinal cohort study
Introduction
Understanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.
Method
Primary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).
Results
We found that 80% had stable NPI total âĽ1, 50% had stable modest NPI total âĽ12 and 25% had stable NPI total âĽ24 scores. Very severe NPS (âĽ48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.
Conclusions
We observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.publishedVersio
Frailty in Older Adults with Mild Dementia: Dementia with Lewy Bodies and Alzheimerâs Disease
Introduction: The aim of the study is to describe the frequency of frailty in people with a new diagnosis of mild dementia due to Alzheimerâs disease (AD) and dementia with Lewy bodies (DLB).
Methods: This is a secondary analysis of the Dementia Study of Western Norway (Demvest). For this study, we analysed a sample of 186 patients, 116 with AD and 70 with DLB. Subjects were included at a time in which mild dementia was diagnosed according to consensus criteria after comprehensive standardized assessment. Frailty was evaluated retrospectively using a frailty index generated from existing data. The cut-off value used to classify an older adult as frail was 0.25.
Results: The prevalence of frailty was 25.81% (n = 48). In the DLB group, 37.14% (n = 26) were classified as frail, compared to 18.97% (n = 22) of those with AD (p < 0.001). The adjusted multivariate analysis revealed an OR of 2.45 (1.15â5.23) for being frail in those with DLB when using AD as the reference group.
Conclusion: Frailty was higher than expected in both types of dementia. The prevalence of frailty was higher in those with DLB compared to AD. This new finding underscores the need for a multi-systems approach in both dementias, with a particular focus on DLB
Cognitive deficits in chronic stroke patients: neuropsychological assessment, depression, and self-reports
Background: Following stroke, clinicians are challenged to detect and untangle symptoms of cognitive dysfunction and mood disorders. Additionally, they need to evaluate the informative value of self-reports to identify patients in need of further attendance. Aims: To examine the association between neuropsychological measures, symptoms of depression, and self-reported cognitive function. Methods: One-hundred and five chronic stroke patients underwent assessment covering 6 cognitive domains and answered the Hospital Anxiety and Depression Scale and the Memory and Thinking Scale from the Stroke Impact Scale 1 year after stroke. Age and gender difference in cognitive impairment were examined; linear regression was used to predict depression scores. Sensitivity and specificity analyses were used to validate self-reported functioning against performance on cognitive tests. Results: Cognitive impairment was observed in 60% of the patients in at least 1 cognitive domain. Cognitive performance was associated with symptoms of depression as well as with self-reported cognitive function. The final analyses revealed low sensitivity and specificity for the Memory and Thinking subscale from the Stroke Impact Scale. Conclusion: Cognitive impairment occurs frequently even in patients in a chronic phase after stroke and predicts symptoms of depression. Using the Stroke Impact Scale, clinicians should be aware of low sensitivity of self-reported cognitive function
Frailty in Older Adults with Mild Dementia: Dementia with Lewy Bodies and Alzheimerâs Disease
Introduction: The aim of the study is to describe the frequency of frailty in people with a new diagnosis of mild dementia due to Alzheimerâs disease (AD) and dementia with Lewy bodies (DLB). Methods: This is a secondary analysis of the Dementia Study of Western Norway (Demvest). For this study, we analysed a sample of 186 patients, 116 with AD and 70 with DLB. Subjects were included at a time in which mild dementia was diagnosed according to consensus criteria after comprehensive standardized assessment. Frailty was evaluated retrospectively using a frailty index generated from existing data. The cut-off value used to classify an older adult as frail was 0.25. Results: The prevalence of frailty was 25.81% (n = 48). In the DLB group, 37.14% (n = 26) were classified as frail, compared to 18.97% (n = 22) of those with AD (p < 0.001). The adjusted multivariate analysis revealed an OR of 2.45 (1.15â5.23) for being frail in those with DLB when using AD as the reference group. Conclusion: Frailty was higher than expected in both types of dementia. The prevalence of frailty was higher in those with DLB compared to AD. This new finding underscores the need for a multi-systems approach in both dementias, with a particular focus on DLB
Impaired synaptic function is linked to cognition in Parkinson's disease
Objective
Cognitive impairment is frequent in Parkinson's disease, but the underlying mechanisms are insufficiently understood. Because cortical metabolism is reduced in Parkinson's disease and closely associated with cognitive impairment, and CSF amyloidâβ species are reduced and correlate with neuropsychological performance in Parkinson's disease, and amyloidâβ release to interstitial fluid may be related to synaptic activity; we hypothesize that synapse dysfunction links cortical hypometabolism, reduced CSF amyloidâβ, and presynaptic deposits of Îąâsynuclein. We expect a correlation between hypometabolism, CSF amyloidâβ, and the synapse relatedâmarkers CSF neurogranin and Îąâsynuclein.
Methods
Thirty patients with mildâtoâmoderate Parkinson's disease and 26 healthy controls underwent a clinical assessment, lumbar puncture, MRI, 18FâfludeoxyglucoseâPET, and a neuropsychological test battery (repeated for the patients after 2 years).
Results
All subjects had CSF amyloidâβ 1â42 within normal range. In Parkinson's disease, we found strong significant correlations between cortical glucose metabolism, CSF Aβ, Îąâsynuclein, and neurogranin. All PET CSF biomarkerâbased cortical clusters correlated strongly with cognitive parameters. CSF neurogranin levels were significantly lower in mildâtoâmoderate Parkinson's disease compared to controls, correlated with amyloidâβ and Îąâsynuclein, and with motor stage. There was little change in cognition after 2 years, but the cognitive tests that were significantly different, were also significantly associated with cortical metabolism. No such correlations were found in the control group.
Interpretation
CSF Aβ, Îąâsynuclein, and neurogranin concentrations are related to cortical metabolism and cognitive decline. Synaptic dysfunction due to Aβ and Îąâsynuclein dysmetabolism may be central in the evolution of cognitive impairment in Parkinson's disease