Subtle visuomotor difficulties in preclinical <scp>A</scp>lzheimer's disease

Mollica, Maria A.; Navarra, Jordi; Fernández-Prieto, Irune; Olives, Jaume; Tort, Adriá; Valech, Natalia; Coll-Padrós, Nina; Molinuevo, José Luís; Rami, Lorena

doi:10.1111/jnp.12079

Cited by 16 publications

(12 citation statements)

References 58 publications

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“…Further, in a recent study of older adults with preclinical AD (defined by having elevated CSF Aβ indicative of AD, but with unimpaired cognition) Mollica et al (2019) found that the speed and variability (a measure of rhythm) of simple finger tapping tests on a computer keyboard are abnormal in preclinical AD, and the degree of variability correlates with CSF Aβ levels [ 19 ]. These findings support earlier studies that determined hand reaction times correlate highly with CSF Aβ biomarker levels in preclinical AD [ 20 ] and progressively worsen over the AD continuum [ 20 – 22 ]. Additionally, it has been shown that even with unimpaired cognition ApoE4 carriers have been found to have delayed hand reactions compared to non-carriers, suggesting hand movements deteriorate at the very earliest stages of preclinical AD [ 20 ].…”

Section: Introductionsupporting

confidence: 91%

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer’s disease and estimate 5-year risks of cognitive decline and dementia

Alty

Bai

et al. 2022

BMC Neurol

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Background The worldwide prevalence of dementia is rapidly rising. Alzheimer’s disease (AD), accounts for 70% of cases and has a 10–20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust ‘self-testing’ data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. Methods Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. Discussion This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. Trial registration ClinicalTrials.gov Identifier: NCT05194787, 18 January 2022. Retrospectively registered.

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Section: Introductionsupporting

confidence: 91%

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer’s disease and estimate 5-year risks of cognitive decline and dementia

Alty

Bai

et al. 2022

BMC Neurol

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“…Hippocampal volume was smaller in SCD+ than SCD− when using both the CCI and Worry and approached significance for the ECog + Worry definition. Such decreased hippocampal volume is consistent with other SCD studies that included worry ( Scheef et al, 2012 ), and memory clinic consultation ( Kim et al, 2013 , Mollica et al, 2017 ). However, we did not find hippocampal volume group differences when defining SCD+ with the ECog.…”

Section: Discussionsupporting

confidence: 90%

Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline

Morrison

Dadar

Shafiee

et al. 2022

NeuroImage: Clinical

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Background People with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. This project examined whether four common methods of defining SCD yields different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+ ) and without SCD (SCD−). Methods Data from 273 Alzheimer’s Disease Neuroimaging Initiative cognitively normal older adults were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry. Voxel-based logistic regressions were applied to deformation-based morphology results to determine if regional atrophy between SCD− and SCD+ differed by SCD definition. Linear mixed-effects models were used to evaluate differences in future cognitive decline. Results Results varied between the four methods of defining SCD. Left hippocampal grading was more similar to AD in SCD+ than SCD− when using the CCI ( p = .041) and Worry ( p = .021) definitions. The right ( p= .008) and left ( p= .003) superior temporal regions had smaller volumes in SCD+ than SCD−, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment. Conclusion These findings suggest that the various methods used to differentiate between SCD− and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.

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“…Thus, it was expected that, overall, results would exhibit agreement; however there were considerable differences between values obtained on the MCS-A and MCS-B. Some studies have found the informant´s perception of the elderly subject with SCI to be a more reliable predictor of cognitive impairment than the elderly subject´s report 11 , 36 - 38. The SCI, when not associated with objective memory alteration, may reflect a distorted awareness of the current cognitive state compared to the past.…”

Section: Discussionmentioning

confidence: 99%

Subjective cognitive impairment, cognitive disorders and self-perceived health: The importance of the informant

Almeida

Dalpubel

Ribeiro

et al. 2019

Dement. neuropsychol.

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There is great divergence of results in the literature regarding the clinical relevance and etiology of subjective cognitive impairment (SCI). Currently, SCI is studied as a pre-clinical symptom of Alzheimer's disease, before establishing a possible diagnosis of mild cognitive impairment (MCI). The hypothesis was that SCI is associated with low cognitive performance and poor self-perceived health. Objective: to investigate the relationship of SCI with objective cognitive impairment and self-perceived health in older individuals and to compare SCI reported by the elderly subjects and by their respective informants. Methods: 83 subjects participated in the study, divided between the forms of the Memory Complaint Scale (MCS). Cognition was evaluated by the Addenbrooke's Cognitive Examination - Revised and self-perceived health by the Short Form Health Survey-8. Results: there was no association between SCI and self-perceived health. SCI reported by the older adults was associated with executive functions. SCI reported by the informant was associated with overall cognitive performance, memory, verbal fluency and visuospatial functions. Conclusion: we found more robust results between SCI reported by the informant and cognitive impairment in the elderly assessed. There is a need to include and value the perception of someone who knows the older individual well enough to evaluate SCI globally.

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Subtle visuomotor difficulties in preclinical Alzheimer's disease

Abstract: The VMC task is able to discriminate Pre-AD from CTR individuals. Moreover, VMC results are associated with AB42 levels in CN individuals, suggesting that visuomotor dysfunction may be a sensitive marker of Pre-AD.

Cited by 16 publications

References 58 publications

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer’s disease and estimate 5-year risks of cognitive decline and dementia

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer’s disease and estimate 5-year risks of cognitive decline and dementia

Regional brain atrophy and cognitive decline depend on definition of subjective cognitive decline

Subjective cognitive impairment, cognitive disorders and self-perceived health: The importance of the informant

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