| 1. |
- Schaefer, Simona, et al.
(författare)
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Screening for Mild Cognitive Impairment Using a Machine Learning Classifier and the Remote Speech Biomarker for Cognition: Evidence from Two Clinically Relevant Cohorts
- 2023
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Ingår i: JOURNAL OF ALZHEIMERS DISEASE. - 1387-2877 .- 1875-8908. ; 91:3, s. 1165-1171
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Tidskriftsartikel (refereegranskat)abstract
- Background: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. Objective: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. Methods: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (N= 121) and a Swedish birth cohort (N= 404). MCI classification was each evaluated on the training cohort as well as on the unrelated validation cohort. Results: The algorithms achieved a performance of AUC similar to 0.73 and AUC similar to 0.77 in the respective training cohorts and AUC similar to 0.81 in the unseen validation cohorts. Conclusion: The results indicate that a ki:e SB-C based algorithm robustly detectsMCIacross different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.
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| 2. |
- Arvidsson Rådestig, Maya, et al.
(författare)
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Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer's Disease: Results from the Gothenburg H70 Birth Cohort Studies.
- 2021
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 79:1, s. 225-235
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that older adults with preclinical Alzheimer's disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology.We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology.The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n=316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories.Among participants with CDR 0 (n=259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p=0.003), object Delayed (p=0.042) and Immediate recall (p=0.033)). Among participants with CDR 0.5 (n=57), those with amyloid pathology (A+) scored worse in category fluency (p=0.003).Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.
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| 3. |
- Arvidsson Rådestig, Maya, et al.
(författare)
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Subtle Differences in Cognition in 70-Year-Olds with Elevated Cerebrospinal Fluid Neurofilament Light and Neurogranin: A H70 Cross-Sectional Study
- 2023
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 91:1, s. 291-303
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most research on cerebrospinal fluid (CSF) neurofilament light protein (NfL) as a marker for neurodegeneration and neurogranin (Ng) for synaptic dysfunction has largely focused on clinical cohorts rather than population-based samples. Objective: We hypothesized that increased CSF levels of NfL and Ng are associated with subtle cognitive deficits in cognitively unimpaired (CU) older adults. Methods: The sample was derived from the Gothenburg H70 Birth Cohort Studies and comprised 258 CU 70-year-olds, with a Clinical Dementia Rating score of zero. All participants underwent extensive cognitive testing. CSF levels of NfL and Ng, as well as amyloid beta(1-42), total tau, and phosphorylated tau, were measured. Results: Participants with high CSF NfL performed worse in one memory-based test (Immediate recall, p = 0.013) and a language test (FAS, p = 0.016). Individuals with high CSF Ng performed worse on the memory-based test Supra Span (p = 0.035). When stratified according to CSF tau and A beta(42) concentrations, participants with high NfL and increased tau performed worse on a memory test than participants normal tau concentrations (Delayed recall, p = 0.003). In participants with high NfL, those with pathologic A beta(42) concentrations performed worse on the Delayed recall memory (p = 0.044). In the high Ng group, participants with pathological A beta(42) concentrations had lower MMSE scores (p = 0.027). However, in regression analysis we found no linear correlations between CSF NfL or CSF Ng in relation to cognitive tests when controlled for important co-variates. Conclusion: Markers of neurodegeneration and synaptic pathology might be associated with subtle signs of cognitive decline in a population-based sample of 70-year-olds.
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| 4. |
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| 5. |
- Eckerström, Marie, 1981, et al.
(författare)
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High Prevalence of Stress and Low Prevalence of Alzheimer Disease CSF Biomarkers in a Clinical Sample with Subjective Cognitive Impairment
- 2016
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 42:1-2, s. 93-105
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Subjective cognitive impairment (SCI) is a trigger for seeking health care in a possible preclinical phase of Alzheimer's disease (AD), although the characteristics of SCI need clarification. We investigated the prevalence of psychosocial stress, depressive symptoms and CSF AD biomarkers in SCI and MCI (mild cognitive impairment). Methods: Memory clinic patients (SCI: n = 90; age: 59.8 ± 7.6 years; MCI: n = 160; age: 63.7 ± 7.0 years) included in the Gothenburg MCI study were examined at baseline. Variables were analyzed using logistic regression with SCI as dependent variable. Results: Stress was more prevalent in SCI (51.1%) than MCI (23.1%); p < 0.0005. SCI patients had more previous depressive symptoms (p = 0.006), but showed no difference compared to MCI patients considering current depressive symptoms. A positive CSF AD profile was present in 14.4% of SCI patients and 35.0% of MCI patients (p = 0.001). Stress (p = 0.002), previous stress/depressive symptoms (p = 0.006) and a negative CSF AD profile (p = 0.036) predicted allocation to the SCI group. Conclusion: Psychosocial stress is more prevalent in SCI than previously acknowledged. The high prevalence and long-term occurrence of stress/depressive symptoms in SCI in combination with a low prevalence of altered CSF AD biomarkers strengthens the notion that AD is not the most likely etiology of SCI.
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| 6. |
- Eckerström, Marie, 1981, et al.
(författare)
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Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:8, s. 96-107
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Tidskriftsartikel (refereegranskat)abstract
- Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications.Memory clinic patients (n=235) were classified as SCD (n=122): subtle cognitive decline (n=36) and mild cognitive impairment (n=77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications.Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage2.In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.
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| 7. |
- Gonzales, Mitzi M., et al.
(författare)
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Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment
- 2018
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Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 33:10, s. 1305-1311
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the association between chronic subsyndromal symptoms of depression (SSD), cerebrospinal fluid (CSF) biomarkers, and neuropsychological performance in individuals with mild cognitive impairment (MCI). Methods: Participants included 238 older adults diagnosed with MCI from the Alzheimer's Disease Neuroimaging Initiative repository with cognitive and CSF amyloid beta (Aβ1–42), total tau (t-tau), and phosphorylated tau (p-tau) data. The Neuropsychiatric Inventory identified individuals with chronic endorsement (SSD group N = 80) or no endorsement (non-SSD group N = 158) of depressive symptoms across timepoints. CSF biomarker and cognitive performance were evaluated with linear regression models adjusting for age, education, gender, APOE genotype, global cognitive status, and SSD group. Results: As compared to the non-SSD group, the SSD group displayed lower CSF Aβ1–42 levels (β = −24.293, S.E. = 6.345, P < 0.001). No group differences were observed for CSF t-tau (P = 0.497) or p-tau levels (P = 0.392). Lower CSF Aβ1–42 levels were associated with poorer performance on learning (β = 0.041, S.E. = 0.018, P = 0.021) and memory (β = −0.012, S.E. = 0.005, P = 0.031) measures, whereas higher CSF t-tau levels were associated with poorer performance on measures of global cognition (β = 0.022, S.E = 0.008, P = 0.007) and language (β = −0.010, S.E = 0.004, P = 0.019). SSD was independently associated with diminished global cognition, learning and memory, language, and executive function performance over and above the effects of CSF biomarkers (all P < 0.05). Conclusions: MCI participants with SSD displayed diminished CSF Aβ1–42 levels but did not differ from non-SSD controls in CSF tau levels. Additionally, CSF biomarkers and SSD independently accounted for variance in cognitive performance, suggesting that these factors may uniquely confer cognitive risk in MCI.
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| 8. |
- Gonzales, M. M., et al.
(författare)
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Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression
- 2017
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Ingår i: American Journal of Geriatric Psychiatry. - : Elsevier BV. - 1064-7481. ; 25:9, s. 980-991
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. Design: Prospective cohort study. Setting: Multicenter, cwere observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. Conclusions: Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy.linic-based. Participants: Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. Measurements: Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. Results: The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences
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| 9. |
- Johansson, Lena, 1972, et al.
(författare)
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Longstanding psychological stress in relation to biomarkers of neuronal dysfunction in cerebrospinal fluid: a 25-year follow-up study in women
- 2019
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 80, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- Longstanding psychological stress has been associated with increased risk of neurodegenerative disorders, such as dementia and Alzheimer's disease. In a prospective population study of women (n = 81), we tested if midlife stress (mean age 49 years) was associated with late-life biomarkers of neuro-degeneration in cerebrospinal fluid (CSF) (mean age 74 years) in linear regression models. It was found that women who report of stress at baseline (n = 20) had higher levels of CSF visinin-like protein-1 (VILIP-1) (age adjusted beta = 0.113, p = 0.017) and CSF myelin basic protein (beta = 0.060, p = 0.030) compared with women without midlife stress (n = 61). There was also a trend observed for higher CSF neurofilament light (beta = 0.133, p = 0.056). In addition, longer periods of stress (i.e., stress at 2-3 midlife examinations) were associated with higher levels of CSF VILIP-1. The results suggest that longstanding stress might be associated with neurodegenerative processes in the brain, as CSF VILIP-1 is an unspecific marker for neuronal injury and CSF myelin basic protein reflects neuroaxonal demyelination. (C) 2019 Elsevier Inc. All rights reserved.
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| 10. |
- Johansson, Lena, 1972, et al.
(författare)
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Longstanding smoking associated with frontal brain lobe atrophy: a 32-year follow-up study in women
- 2023
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Ingår i: BMJ OPEN. - 2044-6055. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo examine the association between midlife tobacco smoking and late-life brain atrophy and white matter lesions.MethodsThe study includes 369 women from the Prospective Population Study of Women in Gothenburg, Sweden. Cigarette smoking was reported at baseline 1968 (mean age=44 years) and at follow-up in 1974-1975 and 1980-1981. CT of the brain was conducted 32 years after baseline examination (mean age=76 years) to evaluate cortical atrophy and white matter lesions. Multiple logistic regressions estimated associations between midlife smoking and late-life brain lesions. The final analyses were adjusted for alcohol consumption and several other covariates.ResultsSmoking in 1968-1969 (adjusted OR 1.85; 95% CI 1.12 to 3.04), in 1974-1975 (OR 2.37; 95% CI 1.39 to 4.04) and in 1980-1981 (OR 2.47; 95% CI 1.41 to 4.33) were associated with late-life frontal lobe atrophy (2000-2001). The strongest association was observed in women who reported smoking at all three midlife examinations (OR 2.63; 95% CI 1.44 to 4.78) and in those with more frequent alcohol consumption (OR 6.02; 95% CI 1.74 to 20.84). Smoking in 1980-1981 was also associated with late-life parietal lobe atrophy (OR 1.99; 95% CI 1.10 to 3.58). There were no associations between smoking and atrophy in the temporal or occipital lobe, or with white matter lesions.ConclusionLongstanding tobacco smoking was mainly associated with atrophy in the frontal lobe cortex. A long-term stimulation of nicotine receptors in the frontal neural pathway might be harmful for targeted brain cell.
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