The effects of normal aging on amyloid‐β deposition in nondemented adults with Down syndrome as imaged by carbon 11–labeled Pittsburgh compound B

Abstract

Introduction In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology. Methods PET imaging with [11C]PiB examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellum as the reference region. Results Multiple linear regression revealed slight but highly significant (corrected p<0.05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex. Conclusion There is an age-related amyloid-β deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.

Outcome Measures for Clinical Trials in Down Syndrome

“…AD-related neuropathological changes occur years to decades prior to the clinical presentation of AD both within the general population (e.g., (Aizenstein et al, 2008)) and in adults with DS (e.g., (S. L. Hartley et al, 2014; Lao et al, 2015; Rafii et al, 2015)). The identification of biomarkers of these pre-symptomatic neuropathological changes, such as amyloid plaques and intracellular neurofibrillary tangles composed of the protein tau, is essential for evaluating disease-modifying treatments and several research groups are presently active in this endeavor.…”

“…The earliest declines associated with MCI-DS and early stage AD have generally been found in episodic memory, executive functioning, and visuospatial processing (Devenny, Krinsky-McHale, Sersen, & Silverman, 2000; Krinsky-McHale, Devenny, & Silverman, 2002), with some evidence of early psychiatric/behavioral changes (Ball et al, 2006; Urv, Krinsky-McHale, & Zigman, 2007). Early mild declines in motor functioning have been under-studied, but are suggested based on early amyloid-β deposition (Lao et al, 2015). Complete MCI-DS and AD assessment should include memory and learning, executive functioning, psychiatric/ behavioral problems, language, and motor performance.…”

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome

“…Analyses then examined the association between change in neuropsychological measures (from Cycle 1 to Cycle 2) and change in both global and AVS-only PiB retention (from Cycle 1 to Cycle 2) as a continuous variable, without controlling for chronological age (Pearson correlations) and then controlling for chronological age (multiple linear regressions). The AVS was analyzed individually because this region reveals the earliest presence of elevated PiB binding in the DS population (Annus et al, 2016; Hartley et al, 2014; Nelson et al, 2011; Lao et al, 2016). Finally, one-way analyses of variance (ANOVAs) and Bonferroni-corrected post-hoc comparisons examined differences in neuropsychological measures by PiB categorization status (consistently PiB−, consistently PiB+, and converted from PiB− to PiB+).…”

“…In addition to assessing neocortical PiB retention, we examined PiB retention in the striatum, as it is the brain region with the earliest amyloid-β accumulation in the DS population (Annus et al, 2016; Lao et al, 2016). PiB retention was evaluated as both a continuous variable and dichotomous variable by categorizing adults with DS as PiB + versus PiB−, in line with previous studies (Annus et al, 2016; Hartley et al, 2014; Nelson et al, 2011; Lao et al, 2016). Analyses were conducted with and without controlling for chronological age to separate out the effects of normative aging from those of amyloid-β accumulation.…”

Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population

“…An interesting finding in individuals with ADAD is the striatum-dominant pattern of amyloid accumulation, regardless of mutation type [11], [12]. In our previous cross-sectional study in the nondemented DS population, patterns of carbon 11-labeled Pittsburgh compound B ([ 11 C]PiB) binding demonstrated the elevated striatal binding in the absence of elevated neocortical binding [13]. These data suggest that a striatum-dominant pattern of amyloid-β plaque deposition in ADAD and DS may be a result of amyloid overproduction, consistent with other work [12], [13], [14], [15], [16].…”