Amyloid PET imaging in patients with mild cognitive impairment

Koivunen, Jaana; Scheinin, Noora M.; Virta, Jere; Aalto, Sargo; Vahlberg, Tero; Någren, Kjell; Helin, Semi; Parkkola, Riitta; Viitanen, Matti; Rinne, Juha O.

doi:10.1212/wnl.0b013e318212015e

Cited by 176 publications

(136 citation statements)

References 18 publications

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“…A study conducted in mainly APOE e4 allele carriers showed that there was no change over time in Ab deposition in converters and nonconverters to AD. However, hippocampal atrophy was worse in converters than in nonconverters, and increased significantly in both groups, 37 suggesting that a dissociation between neurodegeneration and amyloidosis can occur.…”

Section: Resultsmentioning

confidence: 97%

Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old

et al. 2014

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Objective: To examine the association between brain structural changes and b-amyloid deposition, and incident dementia in 183 elderly subjects without dementia (mean age 85.5 years) 2 years later.Methods: Subjects had a brain structural MRI scan and a PET scan with 11 C-labeled Pittsburgh compound B (PiB) in 2009, and were evaluated clinically in 2011.Results: At baseline evaluation, of the 183 participants (146 cognitively normal [CN]); 37 mild cognitive impairment [MCI]), 139 (76%) were PiB1, had small hippocampal volume (,25th percentile), or had high white matter lesion (WML) volume (.75th percentile). Two years later, 111 (61%) were classified as CN, 51 (28%) as MCI, and 21 (11%) as dementia. At baseline, 51% of the CN participants and 67.5% of the MCI cases were PiB1. Thirty percent of the CN and 51% of the MCI cases had small hippocampi, and 24% of the CN and 40.5% of the MCI cases had abnormal WMLs. Of the 21 participants who progressed to dementia, 20 (95%) had at least one imaging abnormality. Only 3 (14%) were only PiB1, 1 (5%) had only small hippocampi, 1 (5%) had only WMLs, 1 (5%) was biomarker negative, and the other 16 had various pairs of imaging abnormalities. Continuous variables of PiB retention, left and right hippocampal volume, and WML volume were independent predictors of dementia in a logistic regression analysis controlling for age, sex, education level, and Mini-Mental State Examination scores. Conclusions:The prevalence of b-amyloid deposition, neurodegeneration (i.e., hippocampal atrophy), and small vessel disease (WMLs) is high in CN older individuals and in MCI. A combination of 2 or 3 of these factors is a powerful predictor of short-term incidence of dementia. Studies of cognition and neurodegeneration in the oldest-old are important because these individuals are at the highest risk of developing dementia, especially Alzheimer disease (AD). 1 Furthermore, the neurodegenerative process that causes AD begins years before the clinical expression of the syndrome.2-4 The proportion of subjects without dementia who have amyloid deposition detected in vivo is approximately 20% to 30%, 4 with rates up to 65% in those aged 80 years or older. 4,5 Amyloid deposition detected with Pittsburgh compound B (PiB) is associated with the development of AD from mild cognitive impairment (MCI), 6,7 and to MCI or AD from normal cognition. 8 Similarly, low hippocampal volume, as a marker of neurodegeneration, is associated with progression to AD in cognitively normal (CN) subjects and in those with MCI.9 It has been hypothesized that AD pathology starts with amyloid deposition, followed by neuronal loss closer

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Section: Resultsmentioning

confidence: 97%

Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old

et al. 2014

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“…5 PET tracers that bind to the aggregated A␤ peptides offer promise to directly assess fibrillar amyloid pathology both visually and quantitatively. 6,7 Prior studies have found that 11 C-labeled Pittsburgh compound B ( 11 C-PiB)-positive normal subjects and subjects with MCI are more likely to show faster cognitive deterioration than PIB-negative subjects. 3,8 -16 However, the short half-life of 11 C (20 minutes) limits its use as a routine clinical test.…”

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confidence: 99%

Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline

et al. 2012

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Objectives: Florbetapir F 18 PET can image amyloid-␤ (A␤) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting A␤ pathology using florbetapir PET in subjects at risk for progressive cognitive decline. Methods:A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (A␤ϩ) or negative (A␤Ϫ) for pathologic levels of ␤-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.

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“…Dysregulation of axonal transport might be one mechanism underlying this spatial separation (2,30). Importantly, posterior midline cortices (precuneus and PCC) are among the regions with the highest Ab load as observed in PET studies including the current study, and Ab load of the PCC predicts conversion of MCI to AD, which is accompanied by increasing hippocampal atrophy (32). In an animal model, it has been shown that experimentally induced PCC dysfunction leads to functional disconnection with the hippocampus (33).…”

Section: Discussionmentioning

confidence: 49%

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

et al. 2013

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Amyloid-b (Ab) deposition is a pathologic hallmark of Alzheimer disease (AD). Although the typical spatial distribution pattern of Ab deposition in early AD mainly involves regions distant from the hippocampus, the predominant clinical feature is impairment of hippocampusdependent memory. We aimed at elucidating the relationship between neocortical Ab load, regional neuronal function, and memory impairment. Methods: Thirty patients with early AD underwent combined 11 C-Pittsburgh compound B ( 11 C-PIB) and 18 F-FDG PET and memory assessments. Composite measures of hemispheric Ab load were calculated by volume-weighted mean values of neocortical 11 C-PIB binding. Voxelwise 18 F-FDG uptake was used as a measure of regional glucose metabolism reflecting neuronal activity. We investigated the relationship between left-and right-hemispheric Ab load and regional glucose metabolism (voxelwise analyses). In addition, we assessed the correlations of hemispheric Ab load (region-ofinterest-based analyses) and regional glucose metabolism (voxelwise analysis) with memory performance. Analyses were corrected for age and sex. Results: Higher Ab load in the left hemisphere was associated with reduced glucose metabolism of the left medial temporal lobe (MTL; r 2 5 0.38) and correlated with worse wordlist recall (r 5 20.37; partial correlation controlled for sex and age). Furthermore, wordlist recall correlated with regional glucose metabolism in the bilateral MTL and precuneus-posterior cingulate cortex and right lingual gyrus (r 2 5 0.24). Conclusion: We demonstrated an association between the left-hemispheric Ab load and impairment of the left MTL in AD at 2 different levels: regional hypometabolism and verbal memory. This correlation suggests that neocortical amyloid deposition is connected to or even drives neuronal dysfunction and neurodegeneration of the MTL, which is associated with impaired episodic memory processing as a clinical core symptom of AD.Key Words: Alzheimer's disease; episodic memory; positron emission tomography; Pittsburgh compound B; amyloid J Nucl Med 2013; 54:1909 54: -1914 54: DOI: 10.2967 Theamyl oid cascade hypothesis of Alzheimer disease (AD) posits that cortical amyloid-b (Ab) deposition is related to downstream neuronal dysfunction and cognitive impairment (1). Ab plaques presumably do not directly impair cognition but rather promote tau pathology in distant vulnerable neurons, which in turn leads to cognitive deficits (2). Intriguingly and at present not fully understood, the spatial distribution of Ab deposition in early AD mainly involves regions that are distant from the hippocampus, although the predominant clinical feature is impairment of hippocampus-dependent memory (3). With the advent of Ab PET imaging, most commonly using the radiotracer 11 C-Pittsburgh compound B ( 11 C-PIB (4)), quantitative in vivo assessment of the Ab load in the human brain has become feasible. Furthermore, PET imaging of regional cerebral glucose metabolism with 18 F-FDG represents an established marker of neuro...

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Amyloid PET imaging in patients with mild cognitive impairment

Cited by 176 publications

References 18 publications

Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old

Amyloid, neurodegeneration, and small vessel disease as predictors of dementia in the oldest-old

Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline

Amyloid-β Load Predicts Medial Temporal Lobe Dysfunction in Alzheimer Dementia

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