Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer’s disease

Abstract

We investigated whether subtle visuomotor deficits were detectable in familial and sporadic preclinical Alzheimer’s disease. A circle-tracing task – with direct and indirect visual feedback, and dual-task subtraction – was completed by 31 individuals at 50% risk of familial Alzheimer’s disease (19 presymptomatic mutation carriers; 12 non-carriers) and 390 cognitively-normal older adults (members of the British 1946 Birth Cohort, all born during the same week; age range at assessment = 69-71 years), who also underwent β-amyloid-PET/MRI to derive amyloid status (positive/negative), whole brain volume and white matter hyperintensity volume. We compared preclinical Alzheimer’s groups against controls cross-sectionally (mutation carriers vs. non-carriers; amyloid-positive vs. amyloid-negative) on speed and accuracy of circle-tracing and subtraction. Mutation carriers (mean 7 years before expected onset) and amyloid-positive older adults traced disproportionately less accurately than controls when visual feedback was indirect, and were slower at dual-task subtraction. In the older adults, the same pattern of associations was found when considering amyloid burden as a continuous variable (Standardised Uptake Value Ratio). The effect of amyloid was independent of white matter hyperintensity and brain volumes, which themselves were associated with different aspects of performance: greater white matter hyperintensity volume was also associated with disproportionately poorer tracing accuracy when visual feedback was indirect, whereas larger brain volume was associated with faster tracing and faster subtraction. Mutation carriers also showed evidence of poorer tracing accuracy when visual feedback was direct. This study provides the first evidence of visuomotor integration deficits common to familial and sporadic preclinical Alzheimer’s disease, which may precede the onset of clinical symptoms by several years.

Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory

“…All assessments were typically completed on one day, although 62 participants had to have their scans rescheduled for a later date (median interval= 49 days). The neuropsychological battery comprised standard paper-and-pencil tests and more novel computerized tasks 28,43,44,48 , none of which had been administered previously within the NSHD. The study was approved by the Queen Square Research Ethics Committee -London (REC reference 14/LO/1173).…”

Current Trends and Applications of PET/MRI Hybrid Imaging in Neurodegenerative Diseases and Normal Aging

“…Outside of diffusion metrics, white matter hyperintensity volume (WMHV) may represent an important marker of dementia; one group found that greater volumes were associated with poorer tracing accuracy in a circle drawing task within patients that had a Familial Alzheimer’s Disease (FAD) mutation and sporadic Alzheimer’s [ 44 ]. Gray matter volume losses were also found to be weakly to strongly positively correlated with regional hypometabolism within the different lobes depending on the subtype of dementia.…”

Adulthood cognitive trajectories over 26 years and brain health at 70 years of age: findings from the 1946 British Birth Cohort

“…Whilst the two cognitive tests assessed here represent fundamental aspects of fluid ability; speed of processing (visual search speed ( Salthouse, 2000 )) and verbal memory (word list test( Elwood, 1995 )), which are sensitive to age and morbidity-associated decline ( Davis et al., 2017 ), the longitudinal cognitive test battery did not include measures of other cognitive domains such as language due to time constraints. Notably, we have a more detailed neuropsychology assessment in the neuroimaging sub-study (n = 500, age 69-71) and we have previously published on the relationship between the cross-sectional nature of neuropsychology measures with brain health ( Lu et al., 2021 , 2020 , 2019a ). We will be able to assess longitudinal changes in these neuropsychological measures in due course with more testing waves.…”