Neural compensation in older people with brain amyloid-β deposition

Elman, Jeremy A.; Oh, Hwamee; Madison, Cindee; Baker, Suzanne L.; Vogel, Jacob W.; Marks, Shawn; Crowley, Sam; O’Neil, James P.; Jagust, William J.

doi:10.1038/nn.3806

Cited by 168 publications

(145 citation statements)

References 32 publications

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…Furthermore, our observations are consistent with the evidence of increased metabolism and CBF at some point in the pathogenesis of AD that is later followed by a phase of reduced CBF (Ostergaard et al, 2013;Thambisetty et al, 2010). Hypermetabolism could be a compensatory mechanism (Elman et al, 2014) (Mormino et al, 2012) or simply an indicator of aberrant neuronal activity as a consequence of amyloid deposition (Kellner et al, 2014;Sperling et al, 2009). Conversely, abberant neuronal activity could promote amyloid deposition (Bero et al, 2011;Cirrito et al, 2005).…”

Section: Association Of Age With Epib As An Estimate Of Rcbf In Pibposupporting

confidence: 88%

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

Gietl¹,

Warnock²,

Riese³

et al. 2015

Neurobiology of Aging

View full text Add to dashboard Cite

Early uptake of [(11)C]-Pittsburgh Compound B (ePiB, 0-6 minutes) estimates cerebral blood flow. We studied ePiB in 13 PiB-negative and 10 PiB-positive subjects with mild cognitive impairment (MCI, n = 23) and 11 PiB-positive and 74 PiB-negative cognitively healthy elderly control subjects (HCS, n = 85) in 6 bilateral volumes of interest: posterior cingulate cortex (PCC), hippocampus (hipp), temporoparietal region, superior parietal gyrus, parahippocampal gyrus (parahipp), and inferior frontal gyrus (IFG) for the associations with cognitive status, age, amyloid deposition, and apolipoprotein E ε4-allele. We observed no difference in ePiB between PiB-positive and -negative subjects and carriers and noncarriers. EPiB decreased with age in PiB-positive subjects in bilateral superior parietal gyrus, bilateral temporoparietal region, right IFG, right PCC, and left parahippocampal gyrus but not in PiB-negative subjects. MCI had lower ePiB than HCS (left PCC, left IFG, and left and right hipp). Lowest ePiB values were found in MCI of 70 years and older, who also displayed high cortical PiB binding. This suggests that lowered regional cerebral blood flow indicated by ePiB is associated with age in the presence but not in the absence of amyloid pathology.

show abstract

Section: Association Of Age With Epib As An Estimate Of Rcbf In Pibposupporting

confidence: 88%

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

Gietl¹,

Warnock²,

Riese³

et al. 2015

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…This interpretation is consistent with recent evidence suggesting compensatory task-induced hyperactivation in CN persons with increased amyloid-β load [26] as well as with the earlier findings on overrecruitment of brain areas associated with word retrieval in CN elderly persons [17]. Assuming that the research model of AD as a continuum that begins with cerebral amyloidosis is on the right track, and given that preclinical AD is heterogeneous [14], two questions are pending.…”

Section: Introductionsupporting

confidence: 88%

An Emerging Model of Word Retrieval in Preclinical Alzheimer ’s Disease

Kljajević¹

2016

J Alzheimers Dis Parkinsonism

View full text Add to dashboard Cite

IntroductionWord retrieval deficit in persons on the Alzheimer's disease (AD) spectrum [1] has been investigated mostly in AD dementia and, to a smaller degree, in patients with mild cognitive impairment (MCI). In contrast, word retrieval abilities in persons at the presumably earliest stage of AD, i.e. in preclinical AD have not been systematically investigated so far. Even though these persons do not present with cognitive symptoms characteristic of MCI and AD, they do exhibit subtle cognitive changes and changes in brain activation patterns [2]. Therefore, the preclinical stage of AD is a unique window into the earliest dynamics of cognitive deterioration emerging under the burden of Alzheimer's pathology.One particularly intriguing question regarding initial cognitive deterioration in AD is how the ability to retrieve words from memory relates to structural and functional changes that have already taken place in the brain at this presumably earliest point in the AD trajectory. Among the brain changes that have been associated with preclinical AD are increased cortical levels of the amyloid-β (Aβ) protein and decreasedCSF amyloid levels together with high levels of tau proteins, considerable temporo-parietal hypometabolism spreading to the frontal lobe, less pronounced grey matter volume reductions and cortical thinning, changes in white matter integrity, and aberrant resting-state functional connectivity patterns [2][3][4][5][6]. This phase of illness may take more than 10 years [7] and "losing words" may begin at any point during this time. When and how this happens is currently not clear.One part of the problem pertains to the fact that word retrieval is a complex process that requires fine-tuning of memory, attention, and language processes. Current theories of the human word-store postulate that the mental lexicon contains information on words' meanings (semantics), their role in a sentence (syntax), and what they sound like (phonology). The mental lexicon of a normal adult literate person contains 50-100 thousand words. The average rate of word production is 2-3 words per second, with only one or two errors occurring in 1000 words [8]. Most researchers agree that retrieving a word from the mental lexicon requires a preliminary conceptual step, followed by a lexical selection (which means access to semantic and syntactic features of the target word), and retrieval of its phonological code, with further steps involving the specifics leading to the word's articulation [9,10]. AbstractWord retrieval deficit in persons on the Alzheimer's disease (AD) spectrum has been investigated mostly in AD dementia and, to a smaller degree, in patients with mild cognitive impairment. However, recent evidence suggests that changes in word retrieval abilities are also present in persons at the presumably earliest stage of AD, i.e. in preclinical AD. Considering this evidence as well as previous findings on word retrieval difficulties in cognitively healthy elderly persons, the present paper outlines a novel model of word ...

show abstract

“…Two early studies found that the subgroup of low performing older adults, failed to show enhanced prefrontal activity characteristic of the high-performing older subgroup (Cabeza et al, 2004;Rosen, Prull, O'Hara, Race, Desmond, Glover, Yesavage, & Gabrieli, 2002) along with prefrontal underactivation relative to the younger adult sample (Rosen et al, 2002). More recently, compensatory over-activity of cortical regions, including prefrontal sites, has been linked to preserved memory performance in older adults who have elevated levels of beta amyloid, a biomarker for AD (Mormino et al, 2012;Elman et al, 2014). This finding suggests that recruitment of prefrontal and other cortical regions may provide computational support that can overcome the compromising effects of amyloid deposition.…”

Section: Neuropsychological Aging and Imaging Brain Functionmentioning

confidence: 99%