Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement

Abstract

Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in patients with Alzheimer's disease. Dynamic [(11)C]Pittsburgh compound-B (90 min) and static [(18)F]fluorodeoxyglucose (15 min) scans were obtained in 100 patients with Alzheimer's disease and 20 healthy controls. Parametric non-displaceable binding potential images of [(11)C]Pittsburgh compound-B and standardized uptake value ratio images of [(18)F]fluorodeoxyglucose were generated using cerebellar grey matter as reference tissue. Nine [(11)C]Pittsburgh compound-B-negative patients were excluded. The remaining patients were categorized into younger (n=45, age: 56 ± 4 years) and older (n=46, age: 69 ± 5 years) groups, based on the median age (62 years) at time of diagnosis. Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (P<0.05), while we found a trend towards poorer memory performance for older patients (P=0.11). Differences between groups were assessed using a general linear model with repeated measures (gender adjusted) with age as between subjects factor, region (frontal, temporal, parietal and occipital and posterior cingulate cortices) as within subjects factor and [(11)C]Pittsburgh compound-B binding/[(18)F]fluorodeoxyglucose uptake as dependent variables. There was no main effect of age for [(11)C]Pittsburgh compound-B or [(18)F]fluorodeoxyglucose, suggesting that overall, the extent of amyloid deposition or glucose hypometabolism did not differ between groups. Regional distributions of [(11)C]Pittsburgh compound-B binding and [(18)F]fluorodeoxyglucose uptake (both P for interaction <0.05) differed between groups, however, largely due to increased [(11)C]Pittsburgh compound-B binding and decreased [(18)F]fluorodeoxyglucose uptake in the parietal cortex of younger patients (both P<0.05). Linear regression analyses showed negative associations between visuo-spatial functioning and parietal [(11)C]Pittsburgh compound-B binding for younger patients (standardized β: -0.37) and between visuo-spatial functioning and occipital binding for older patients (standardized β: -0.39). For [(18)F]fluorodeoxyglucose, associations were found between parietal uptake with visuo-spatial (standardized β: 0.55), attention (standardized β: 0.39) and executive functioning (standardized β: 0.37) in younger patients, and between posterior cingulate uptake and memory in older patients (standardized β: 0.41, all P<0.05). These in vivo findings suggest that clinical differences between younger and older patients with Alzheimer's disease are not restricted to topographical differentiation in downstream processes but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, i...

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

“…These clinical variants include posterior cortical atrophy (PCA, 'visual variant of Alzheimer's disease'; Crutch et al, 2012), logopenic variant primary progressive aphasia (logopenic variant PPA, 'language variant of Alzheimer's disease'; Gorno-Tempini et al, 2011), corticobasal syndrome (Alzheimer's disease pathology is the causative pathology in up to 25% of cases; Dickson et al, 2002;Lee et al, 2011), and memorypredominant and behavioural/dysexecutive variants of Alzheimer's disease (Ossenkoppele et al, 2015c). Age at onset has also been associated with clinical and anatomical variability; while patients with late-onset Alzheimer's disease (565 years of age) typically present with amnestic symptoms and medial temporal lobe neurodegeneration, patients with early-onset (565 years) tend to exhibit greater non-amnestic deficits and neocortical-predominant atrophy (Rabinovici et al, 2010;Mendez et al, 2012;Ossenkoppele et al, 2012;Smits et al, 2012;Moller et al, 2013;Cavedo et al, 2014). Furthermore, patients with Alzheimer's disease who carry the apolipoprotein E (APOE) e4 allele have shown greater medial temporal lobe vulnerability (Pievani et al, 2009;van der Flier et al, 2011;Ossenkoppele et al, 2013b;Lehmann et al, 2014) and post-mortem tau pathology (Beffert and Poirier, 1996;Tiraboschi et al, 2004) compared to non-carriers.…”

Clinical Neurophysiological and Automated EEG-Based Diagnosis of the Alzheimer's Disease

“…It affects cognition, thought process, learning Early onset of AD is seen in people between 30 and 60 years of age due to inherited genes in an autosomal-dominant manner [15,16] . The younger population with early-onset AD possesses a distinct cognitive profile reflecting different distribution of underlying neuropathology [17] . Ossenkoppele et al [17] observed that increased amyloid-beta (Aβ) deposition in the parietal lobe and metabolic dysfunction contribute to the distinct cognitive profile of patient's with AD.…”

“…The younger population with early-onset AD possesses a distinct cognitive profile reflecting different distribution of underlying neuropathology [17] . Ossenkoppele et al [17] observed that increased amyloid-beta (Aβ) deposition in the parietal lobe and metabolic dysfunction contribute to the distinct cognitive profile of patient's with AD.…”

Cortical Functional Connections and Fluid Intelligence in Adolescent APOE ε4 Carriers

“…2). Ossenkoppele et al [15] reported that a greater amyloid burden and modest metabolic dysfunction in the parietal cortex shown in younger AD patients is related to cognitive deficits such as acalculia, spatial disorientation, and apraxia [16]. Importantly, the ε4 allele predisposes to beginning β-amyloid accumulation [17], and to decreasing signals in the parietal association brain areas earlier in life [18].…”