Association Between Visual Memory andIn VivoAmyloid and Tau Pathology in Preclinical Autosomal Dominant Alzheimer’s Disease

Abstract

Objective: Visual memory (ViM) declines early in Alzheimer’s disease (AD). However, it is unclear whether ViM impairment is evident in the preclinical stage and relates to markers of AD pathology. We examined the relationship between ViM performance and in vivo markers of brain pathology in individuals with autosomal dominant AD (ADAD). Methods: Forty-five cognitively unimpaired individuals from a Colombian kindred with the Presenilin 1 (PSEN1) E280A ADAD mutation (19 carriers and 26 noncarriers) completed the Rey–Osterrieth Complex Figure immediate recall test, a measure of ViM. Cortical amyloid burden and regional tau deposition in the entorhinal cortex (EC) and inferior temporal cortex (IT) were measured using 11C-Pittsburgh compound B positron emission tomography (PET) and 11F-flortaucipir PET, respectively. Results: Cognitively unimpaired carriers and noncarriers did not differ on ViM performance. Compared to noncarriers, carriers had higher levels of cortical amyloid and regional tau in both the EC and IT. In cognitively unimpaired carriers, greater cortical amyloid burden, higher levels of regional tau, and greater age were associated with worse ViM performance. Only a moderate correlation between regional tau and ViM performance remained after adjusting for verbal memory scores. None of these correlations were observed in noncarriers. Conclusions: Results suggest that AD pathology and greater age are associated with worse ViM performance in ADAD before the onset of clinical symptoms. Further investigation with larger samples and longitudinal follow-up is needed to examine the utility of ViM measures for identifying individuals at high risk of developing dementia later in life.

Neuropsychological profile in the preclinical stages of dementia: principal component analysis approach

“…However, participants with MCI showed a tendency to have lower scores after more years of education. These results are consistent with other studies where changes in memory and visuospatial skills have been corroborated with the presence of CSF biomarkers 40 or in patients with genetic mutation, 39 showing greater deposits of tau protein and beta-amyloid in the entorhinal areas, connected with hippocampal and parietal medium structures. 41 Additionally, some studies 17 , 42 revealed a decrease in measurements of episodic memory and visuoconstruction in participants with SCD.…”

“…These results allow distinguishing the participants with normal cognition and SCD from the participants with MCI in memory and visuoconstructional processes, as demonstrated by other studies. 25 , 39 But they also allow to see the tendency in the progressive decline during these phases seemingly unaffected by age and years of education. However, participants with MCI showed a tendency to have lower scores after more years of education.…”

Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease

“…Carriers showed an association between visual memory performance and AD pathology in vivo, evaluated by positron emission tomography (PET). 52 We also found that in PSEN1 E280A FAD patients, a cluster of genes localized in chromosomes 6 and 11 showed highly statistically significant association to visual memory decline, as evaluated by R-OFR, and to memory decline in general. The 6p21.33 region showed five genes (i.e., DDR1, GTF2H4, VARS2, DPCR1, and SFTA2) strongly asso-ciated to memory performance.…”

Cortical thickness across the lifespan in a Colombian cohort with autosomal‐dominant Alzheimer's disease: A cross‐sectional study

“…The medial temporal lobe is particularly vulnerable to early tau deposition in this ADAD cohort 27 and sporadic AD 28 . All of the aforementioned brain regions are susceptible to neurodegeneration early in ADAD due to PSEN1 E280A, and many are also implicated in memory encoding and retrieval processes, which are early cognitive symptoms of AD 29,30 . Relative to non‐carriers, we also found significantly stronger positive associations between the AD cortical thickness signature and memory performance in all adult carriers (and at trending significance in cognitively unimpaired carriers), suggesting a deleterious impact of lower cortical thickness on cognitive performance in preclinical and early symptomatic ADAD.…”