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  • 1
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 2
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy. An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population. We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 3
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 4
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 1 ( 2023-01-13), p. e2250921-
    Abstract: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. Objective To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. Design, Setting, and Participants This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. Exposures Disclosure of amyloid-PET result. Main Outcomes and Measures Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale–Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). Results After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30] ) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2] ; P   & amp;lt; .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00] ; P   & amp;lt; .001), IES-R intrusions (0.50 [0.13 to 0.75] vs 0.00 [0.00 to 0.25] ; P   & amp;lt; .001), and IES-R hyperarousal (0.33 [0.00 to 0.67] vs 0.00 [0.00 to 0.00] ; P   & amp;lt; .001) scores than the 78 patients who were amyloid-negative (median [IQR], age, 67 [64 to 74] years, 45 men [58%], median [IQR] education: 15 [12 to 17] years, median [IQR] MMSE score: 29 [28 to 30]). There were no observed differences between amyloid-positive and amyloid-negative patients in the median (IQR) HADS Anxiety (–1.0 [–3.0 to 1.8] vs –2.0 [–4.8 to 1.0]; P  = .06) and Depression (–1.0 [–2.0 to 0.0] vs –1.0 [–3.0 to 0.0] ; P  = .46) deltas (score after disclosure – scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = –0.43; P  = .02) whereas the presence of study partner was associated with higher disclosure-related distress ( W  = 7.5; P  = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. Conclusions and Relevance The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 5
    In: The Lancet Regional Health - Europe, Elsevier BV, Vol. 26 ( 2023-03), p. 100576-
    Type of Medium: Online Resource
    ISSN: 2666-7762
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 3055963-7
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  • 6
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Subjective cognitive decline (SCD) is the subjective perception of a decline in memory and/or other cognitive functions in the absence of objective evidence. Some SCD individuals however may suffer from very early stages of neurodegenerative diseases (such as Alzheimer’s disease, AD), minor psychiatric conditions, neurological, and/or somatic comorbidities. Even if a theoretical framework has been established, the etiology of SCD remains far from elucidated. Clinical observations recently lead to the hypothesis that individuals with incipient AD may have overestimated metacognitive judgements of their own cognitive performance, while those with psychiatric disorders typically present underestimated metacognitive judgements. Moreover, brain connectivity changes are known correlates of AD and psychiatric conditions and might be used as biomarkers to discriminate SCD individuals of different etiologies. The aim of the COSCODE study is to identify metacognition, connectivity, behavioral, and biomarker profiles associated with different etiologies of SCD. Here we present its rationale and study design. Methods COSCODE is an observational, longitudinal (4 years), prospective clinical cohort study involving 120 SCD, and 80 control study participants (40 individuals with no cognitive impairment, and 40 living with mild cognitive impairment - MCI, or dementia due to AD), all of which will undergo diffusion magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) as well as behavioral and biomarker assessments at baseline and after 1 and 2 years. Both hypothesis-driven and data-driven cluster analysis approaches will be used to identify SCD sub-types based on metacognition, connectivity, behavioral, and biomarker features. Conclusion COSCODE will allow defining and interpreting the constellation of signs and symptoms associated with different etiologies of SCD, paving the way to the development of cost-effective risk assessment and prevention protocols.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 7
    In: European Journal of Nuclear Medicine and Molecular Imaging, Springer Science and Business Media LLC, Vol. 48, No. 7 ( 2021-07), p. 2200-2211
    Abstract: Assess the individual and combined diagnostic value of amyloid-PET and tau-PET in a memory clinic population. Methods Clinical reports of 136 patients were randomly assigned to two diagnostic pathways: AMY-TAU, amyloid-PET is presented before tau-PET; and TAU-AMY, tau-PET is presented before amyloid-PET. Two neurologists independently assessed all reports with a balanced randomized design, and expressed etiological diagnosis and diagnostic confidence (50–100%) three times: (i) at baseline based on the routine diagnostic workup, (ii) after the first exam (amyloid-PET for the AMY-TAU pathway, and tau-PET for the TAU-AMY pathway), and (iii) after the remaining exam. The main outcomes were changes in diagnosis (from AD to non-AD or vice versa) and in diagnostic confidence. Results Amyloid-PET and tau-PET, when presented as the first exam, resulted in a change of etiological diagnosis in 28% ( p  = 0.006) and 28% ( p   〈  0.001) of cases, and diagnostic confidence increased by 18% ( p   〈  0.001) and 19% ( p   〈  0.001) respectively, with no differences between exams ( p   〉  0.05). We observed a stronger impact of a negative amyloid-PET versus a negative tau-PET ( p  = 0.014). When added as the second exam, amyloid-PET and tau-PET resulted in a further change in etiological diagnosis in 6% ( p  = 0.077) and 9% ( p  = 0.149) of cases, and diagnostic confidence increased by 4% ( p   〈  0.001) and 5% ( p   〈  0.001) respectively, with no differences between exams ( p   〉  0.05). Conclusion Amyloid-PET and tau-PET significantly impacted diagnosis and diagnostic confidence in a similar way, although a negative amyloid-PET has a stronger impact on diagnosis than a negative tau-PET. Adding either of the two as second exam further improved diagnostic confidence. Trial number PB 2016-01346.
    Type of Medium: Online Resource
    ISSN: 1619-7070 , 1619-7089
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2098375-X
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  • 8
    In: Nature Reviews Neuroscience, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-01), p. 53-66
    Type of Medium: Online Resource
    ISSN: 1471-003X , 1471-0048
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2028902-9
    SSG: 12
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  • 9
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S5 ( 2020-12)
    Abstract: Advances in the Alzheimer’s disease (AD) field have enhanced awareness on brain health and prevention. This brings an increasing number of adults to ask for help in memory clinics for mild forgetfulness, leading to the increased use of health care resources. Nowadays, about 25% of memory clinics patients complain of cognitive decline in absence of objective deficits (subjective cognitive decline,SCD), and they are expected to increase in the coming years. Some patients with SCD later develop cognitive impairment and dementia, often due to AD, but the majority have psychiatric conditions, physical diseases, polypharmacy, or normal brain ageing. Differentiating these potential causes is often a difficult exercise even for expert physicians. The COSCODE project, funded by Swiss National Science Foundation and led by the Geneva Memory Clinic, aims to identify possible subgroups of SCD and their associated risk of decline. This abstract is focused on the retrospective analyses of SCD patients, to develop and future validate the recruitment criteria and SCD categorization. Methods We included 42 SCD from the Geneva Memory Clinic cohort with the following criteria:(i)Amyloid‐PET;(ii)MRI;(iii)clinical and neuropsychological evaluation;(iv)at least 1 follow‐up planned. To evaluate the representativeness of our sample we assessed the correlation between age, episodic memory and medial temporal lobe atrophy scale; Amyloid SUVr and Episodic memory. Then, a neuropsychologist and a neurologist evaluated the clinical reports in order to identify possible aetiologies of the cognitive complaint. Results In the whole sample (age, mean±SD:71±7years; 54% female; education:16.3±4.1; MMSE:28.8±0.8; 24% A+) age is inversely correlated with episodic memory (Free‐and‐cue‐selective‐reminding‐test, p=0.003) and positively with medial temporal lobe atrophy scale (p=0.017). Amyloid SUVr correlates negatively with episodic memory performance (p 〈 0.05). On the other hands, the clinicians found 3 different aetiologies of the SCD: Comorbidity (stroke, brain injury, cardio‐vascular risk factors, physical disability,...), Psychopathology (depression, anxiety, personality trait); Unknown (apparently, no reason associated to the complaint). The prevalence of the 3 groups is respectively:29%,33%,38%. Conclusions Our SCD sample can be considered representative of a memory clinic population, indeed it’s a very heterogeneous group. The 3 groups categorization will be validated using a data driven approach and studying longitudinal trajectory of each subgroup to better understand their associated risk of decline.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
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  • 10
    In: Alzheimer's & Dementia, Wiley, Vol. 14, No. 7S_Part_28 ( 2018-07)
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2201940-6
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