Search tips
Search criteria

Results 1-13 (13)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features 
Brain  2015;138(9):2732-2749.
Relatively little is known about behavioural- and dysexecutive-predominant presentations of Alzheimer’s disease, collectively known as ‘frontal’ Alzheimer’s disease. Ossenkoppele et al. compare these two syndromes, revealing classical temporoparietal atrophy and relative sparing of frontal cortex in both, and propose that they are redefined as the ‘behavioural/dysexecutive variant of Alzheimer’s disease’.
Relatively little is known about behavioural- and dysexecutive-predominant presentations of Alzheimer’s disease, collectively known as ‘frontal’ Alzheimer’s disease. Ossenkoppele et al. compare these two syndromes, revealing classical temporoparietal atrophy and relative sparing of frontal cortex in both, and propose that they are redefined as the ‘behavioural/dysexecutive variant of Alzheimer’s disease’.
A ‘frontal variant of Alzheimer’s disease’ has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer’s disease pathology. The description of this rare Alzheimer’s disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer’s disease with a behavioural-predominant presentation (behavioural Alzheimer’s disease) and a neuropathological diagnosis of high-likelihood Alzheimer’s disease (n = 17) and/or biomarker evidence of Alzheimer’s disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer’s disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer’s disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer’s disease: 53%; dysexecutive Alzheimer’s disease: 83%) than behavioural (behavioural Alzheimer’s disease: 25%; dysexecutive Alzheimer’s disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer’s disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer’s disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer’s disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer’s disease (typical Alzheimer’s disease, n = 58), autopsy-confirmed/Alzheimer’s disease biomarker-negative behavioural variant frontotemporal dementia (n = 59), and controls (n = 61). Patients with behavioural Alzheimer’s disease showed worse memory scores than behavioural variant frontotemporal dementia and did not differ from typical Alzheimer’s disease, while executive function composite scores were lower compared to behavioural variant frontotemporal dementia and typical Alzheimer’s disease. Voxel-wise contrasts between behavioural and dysexecutive Alzheimer’s disease patients and controls revealed marked atrophy in bilateral temporoparietal regions and only limited atrophy in the frontal cortex. In direct comparison with behavioural and those with dysexecutive Alzheimer’s disease, patients with behavioural variant frontotemporal dementia showed more frontal atrophy and less posterior involvement, whereas patients with typical Alzheimer’s disease were slightly more affected posteriorly and showed less frontal atrophy (P < 0.001 uncorrected). Among 24 autopsied behavioural Alzheimer’s disease/dysexecutive Alzheimer’s disease patients, only two had primary co-morbid FTD-spectrum pathology (progressive supranuclear palsy). In conclusion, behavioural Alzheimer’s disease presentations are characterized by a milder and more restricted behavioural profile than in behavioural variant frontotemporal dementia, co-occurrence of memory dysfunction and high APOE ε4 prevalence. Dysexecutive Alzheimer’s disease presented as a primarily cognitive phenotype with minimal behavioural abnormalities and intermediate APOE ε4 prevalence. Both behavioural Alzheimer’s disease and dysexecutive Alzheimer’s disease presentations are distinguished by temporoparietal-predominant atrophy. Based on the relative sparing of frontal grey matter, we propose to redefine these clinical syndromes as ‘the behavioural/dysexecutive variant of Alzheimer’s disease’ rather than frontal variant Alzheimer’s disease. Further work is needed to determine whether behavioural and dysexecutive-predominant presentations of Alzheimer’s disease represent distinct phenotypes or a single continuum.
PMCID: PMC4623840  PMID: 26141491
Alzheimer’s disease; frontotemporal dementia; frontal, behaviour; executive function
2.  The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer’s disease 
The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer’s disease (AD) patients and healthy elderly controls.
Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [11C]PIB to assess amyloid-β plaque load and [18F]FDG to assess glucose metabolism. [11C]PIB binding and [18F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD.
While amyloid-β plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho=0.56, p<0.05).
The present study shows that in a group of AD patients amyloid-β plaque load as measured by [11C]PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [18F]FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration.
PMCID: PMC4917377  PMID: 24615466
Alzheimer’s disease; Amyloid plaques; Hypometabolism; Atrophy; Longitudinal study
3.  Mild cognitive impairment with suspected nonamyloid pathology (SNAP) 
Neurology  2015;84(5):508-515.
The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non–Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).
We measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18F]-fluorodeoxyglucose–PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A− and N+/N− based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A−N+ cases.
The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A−N−, A+N−, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N− and A+N+ groups (p ≤ 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A−N−, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N− patients did not (hazard ratio = 1.13, p = 0.771). In A+N− and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).
Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.
PMCID: PMC4336071  PMID: 25568301
4.  Atrophy Patterns in Early Clinical Stages Across Distinct Phenotypes of Alzheimer’s Disease 
Human brain mapping  2015;36(11):4421-4437.
Alzheimer’s disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, “visual variant,” n = 93), logopenic variant primary progressive aphasia (lvPPA, “language variant,” n = 74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n = 114) and late age-of-onset (LOAD, >65 years, n = 114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n = 80). Even at the earliest clinical stage (CDR =0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.
PMCID: PMC4692964  PMID: 26260856
Alzheimer’s disease; magnetic resonance imaging (MRI); posterior cortical atrophy; logopenic variant primary progressive aphasia; early-onset dementia; default mode network; language; memory; vision; atrophy; voxel-based morphometry
5.  Prevalence of Amyloid PET Positivity in Dementia Syndromes 
JAMA  2015;313(19):1939-1949.
Amyloid-β positron emission tomography (PET) imaging allows in vivo detection of fibrillar plaques, a core neuropathological feature of Alzheimer disease (AD). Its diagnostic utility is still unclear because amyloid plaques also occur in patients with non–AD dementia.
To use individual participant data meta-analysis to estimate the prevalence of amyloid positivity on PET in a wide variety of dementia syndromes.
The MEDLINE and Web of Science databases were searched from January 2004 to April 2015 for amyloid PET studies.
Case reports and studies on neurological or psychiatric diseases other than dementia were excluded. Corresponding authors of eligible cohorts were invited to provide individual participant data.
Data were provided for 1359 participants with clinically diagnosed AD and 538 participants with non–AD dementia. The reference groups were 1849 healthy control participants (based on amyloid PET) and an independent sample of 1369 AD participants (based on autopsy).
Estimated prevalence of positive amyloid PET scans according to diagnosis, age, and apolipoprotein E (APOE) ε4 status, using the generalized estimating equations method.
The likelihood of amyloid positivity was associated with age and APOE ε4 status. In AD dementia, the prevalence of amyloid positivity decreased from age 50 to 90 years in APOE ε4 noncarriers(86%[95%CI,73%–94%]at 50 years to 68% [95% CI,57%–77%] at 90 years; n = 377) and to a lesser degree in APOE ε4 carriers (97% [95% CI, 92%–99%] at 50 years to 90% [95% CI, 83%–94%] at 90 years; n = 593; P < .01). Similar associations of age and APOE ε4 with amyloid positivity were observed in participants with AD dementia at autopsy. In most non–AD dementias, amyloid positivity increased with both age (from 60 to 80 years) and APOE ε4 carriership. Total ParticipantsAmyloid Positivity, % (95% CI) Age 60 yAge 80 y Dementia with Lewy bodies  emsp;APOE ε4 carrier  1663 (48–80)83 (67–92)  emsp;APOE ε4 noncarrier  1829 (15–50)54 (30–77) Frontotemporal dementia  emsp;APOE ε4 carrier  4819 (12–28)43 (35–50)  emsp;APOE ε4 noncarrier160  5 (3–8)14 (11–18) Vascular dementia  emsp;APOE ε4 carrier  3025 (9–52)64 (49–77)  emsp;APOE ε4 noncarrier  77  7 (3–18)29 (17–43)
Among participants with dementia, the prevalence of amyloid positivity was associated with clinical diagnosis, age, and APOE genotype. These findings indicate the potential clinical utility of amyloid imaging for differential diagnosis in early-onset dementia and to support the clinical diagnosis of participants with AD dementia and noncarrier APOE ε4 status who are older than 70 years.
PMCID: PMC4517678  PMID: 25988463
6.  Is Verbal Episodic Memory in Elderly with Amyloid Deposits Preserved Through Altered Neuronal Function? 
Cerebral Cortex (New York, NY)  2013;24(8):2210-2218.
A potential mechanism that enables intellectual preservation in cognitively normal elderly that harbor beta-amyloid (Aβ) pathology is heightened cerebral glucose metabolism. To investigate cross-sectional inter-relationships between Aβ, glucose metabolism, and cognition, 81 subjects (mean age: 75 ± 7 years) underwent [11C]Pittsburgh Compound-B and [18F]fluorodeoxyglucose positron emission tomography scans and neuropsychological testing. They were divided into low-Aβ (n = 53), intermediate-Aβ (n = 13) and high-Aβ (n = 15) groups as defined by their global cortical [11C]PIB retention. Glucose metabolism was assessed using a MetaROI mask that covers metabolically critical regions in Alzheimer's disease (AD) (i.e., posterior cingulate and bilateral angular and inferior temporal gyri). Previously validated factor scores for verbal and visual episodic memory, semantic memory, working memory, and executive functioning were used to evaluate cognitive performances. Greater Aβ deposition in the precuneus was associated with higher metabolic activity (at trend level) and lower visual episodic memory scores. Glucose metabolism did not correlate with cognition across all subjects. However, heightened metabolic activity was associated with better verbal episodic memory performance in subjects with elevated amyloid levels. This preliminary study suggests that neural compensation, as a manifestation of brain reserve, enables elderly supposedly on the path to AD, at least temporarily, to preserve cognitive function.
PMCID: PMC4089385  PMID: 23537530
aging; [11C]PIB; beta-amyloid; cognition; [18F]FDG; glucose metabolism; PET
7.  Cerebrospinal Fluid Biomarkers and Cerebral Atrophy in Distinct Clinical Variants of Probable Alzheimer’s Disease 
Neurobiology of aging  2015;36(8):2340-2347.
Different clinical variants of probable Alzheimer’s disease (AD) share underlying plaques and tangles but show distinct atrophy patterns. We included 52 posterior cortical atrophy (PCA), 29 logopenic variant primary progressive aphasia (lvPPA), 53 early-onset (EOAD) and 42 late-onset AD (LOAD) patients, selected for abnormal CSF-Aβ42, with CSF and MRI data available. Bootstrapping revealed no differences in the prevalence of abnormal CSF total-tau and phosphorylated-tau between probable AD variants (range total-tau: 84.9–92.3%, phosphorylated-tau: 79.2–93.1%, p>0.05). Voxel-wise linear regressions showed various relationships between lower CSF-Aβ42 and syndrome-specific atrophy, involving precuneus, posterior cingulate, and medial temporal lobe (MTL) in EOAD, occipital cortex and middle temporal gyrus in PCA; anterior cingulate, insular cortex and precentral gyrus (left>right) in lvPPA; and MTL, thalamus, and temporal pole in LOAD (all at p<0.001 uncorrected). In contrast, CSF-tau was not related to gray matter atrophy in any group. Our findings suggest that lower CSF-Aβ42 – and not increased total-tau and phosphorylated-tau – relates to reduced gray matter volumes, mostly in regions that are typically atrophied in distinct clinical variants of probable AD.
PMCID: PMC4465267  PMID: 25990306
Alzheimer’s disease; cerebrospinal fluid; magnetic resonance imaging; amyloid; tau; atrophy
8.  Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia 
JAMA  2015;313(19):1924-1938.
Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).
Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.
Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.
Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.
Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.
The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOEε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOEgenotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
PMCID: PMC4486209  PMID: 25988462
9.  Cerebral perfusion and glucose metabolism in Alzheimer’s disease and frontotemporal dementia: two sides of the same coin? 
European Radiology  2015;25(10):3050-3059.
Alzheimer’s disease (AD) and frontotemporal (FTD) dementia can be differentiated using [18F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD.
Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed.
Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68).
Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET.
Key Points
• Similar patterns of hypoperfusion and hypometabolism were observed in patients with dementia.
• For both imaging modalities, parietal abnormalities were found in Alzheimer’s disease.
• For both imaging modalities, prefrontal abnormalities were found in frontotemporal dementia.
Electronic supplementary material
The online version of this article (doi:10.1007/s00330-015-3696-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4562004  PMID: 25899416
Perfusion MRI; Positron-emission tomography; 18F-FDG; Alzheimer’s disease; Frontotemporal dementia
10.  Tau, Amyloid, and Hypometabolism in a Patient with Posterior Cortical Atrophy 
Annals of neurology  2014;77(2):338-342.
Determining the relative contribution of amyloid plaques and neurofibrillary tangles to brain dysfunction in Alzheimer disease is critical for therapeutic approaches, but until recently could only be assessed at autopsy. We report a patient with posterior cortical atrophy (visual variant of Alzheimer disease) who was studied using the novel tau tracer [18F]AV-1451 in conjunction with [11C]Pittsburgh compound B (PIB; amyloid) and [18F]fluorodeoxyglucose (FDG) positron emission tomography. Whereas [11C]PIB bound throughout association neocortex, [18F]AV-1451 was selectively retained in posterior brain regions that were affected clinically and showed markedly reduced [18F]FDG uptake. This provides preliminary in vivo evidence that tau is more closely linked to hypometabolism and symptomatology than amyloid.
PMCID: PMC4382124  PMID: 25448043
11.  Widespread Disruption of Functional Brain Organization in Early-Onset Alzheimer’s Disease 
PLoS ONE  2014;9(7):e102995.
Early-onset Alzheimer’s disease (AD) patients present a different clinical profile than late-onset AD patients. This can be partially explained by cortical atrophy, although brain organization might provide more insight. The aim of this study was to examine functional connectivity in early-onset and late-onset AD patients. Resting-state fMRI scans of 20 early-onset (<65 years old), 28 late-onset (≥65 years old) AD patients and 15 “young” (<65 years old) and 31 “old” (≥65 years old) age-matched controls were available. Resting-state network-masks were used to create subject-specific maps. Group differences were examined using a non-parametric permutation test, accounting for gray-matter. Performance on five cognitive domains were used in a correlation analysis with functional connectivity in AD patients. Functional connectivity was not different in any of the RSNs when comparing the two control groups (young vs. old controls), which implies that there is no general effect of aging on functional connectivity. Functional connectivity in early-onset AD was lower in all networks compared to age-matched controls, where late-onset AD showed lower functional connectivity in the default-mode network. Functional connectivity was lower in early-onset compared to late-onset AD in auditory-, sensory-motor, dorsal-visual systems and the default mode network. Across patients, an association of functional connectivity of the default mode network was found with visuoconstruction. Functional connectivity of the right dorsal visual system was associated with attention across patients. In late-onset AD patients alone, higher functional connectivity of the sensory-motor system was associated with poorer memory performance. Functional brain organization was more widely disrupted in early-onset AD when compared to late-onset AD. This could possibly explain different clinical profiles, although more research into the relationship of functional connectivity and cognitive performance is needed.
PMCID: PMC4117463  PMID: 25080229
12.  Amyloid imaging in clinical trials 
The possibility to map amyloid-beta, the Alzheimer’s disease hallmark protein, in vivo opens the application for amyloid imaging in clinical trials with disease-modifying agents. Monitoring change in amyloid burden, particularly when potential amyloid-lowering drugs are at play, requires accurate analytical methods. Studies to date have used suboptimal methods that do not account for heterogeneous changes in flow associated with disease progression and potentially with anti-amyloid drugs. In this commentary, we discuss practical and methodological issues regarding longitudinal amyloid imaging and propose several quantitative, yet feasible, alternatives for reliable assessment of changes over time in amyloid burden.
PMCID: PMC3978734  PMID: 23953396
13.  Amyloid imaging in prodromal Alzheimer's disease 
Patients with mild cognitive impairment are at an increased risk of progression to Alzheimer's disease. However, not all patients with mild cognitive impairment progress, and it is difficult to accurately identify those patients who are in the prodromal stage of Alzheimer's disease. In a recent paper, Koivunen and colleagues report that Pittsburgh compound-B, an amyloid-beta positron emission tomography ligand, predicts the progression of patients with mild cognitive impairment to Alzheimer's disease. Of 29 subjects with mild cognitive impairment, 21 (72%) had a positive Pittsburgh compound-B positron emission tomography baseline scan. In their study, 15 of these 21 (71%) patients progressed to Alzheimer's disease, whilst only 1 out of 8 (12.5%) Pittsburgh compound-B-negative patients with mild cognitive impairment did so. Moreover, in these mild cognitive impairment patients, the overall amyloid burden increased approximately 2.5% during the follow-up period. This is consistent with other longitudinal amyloid imaging studies that found a similar increase in amyloid deposition over time in patients with mild cognitive impairment. These studies together challenge current theories that propose a flattening of the increase of brain amyloid deposition already in the preclinical stage of Alzheimer's disease. These findings may have important implications for the design of future clinical trials aimed at preventing progression to Alzheimer's disease by lowering the brain amyloid-beta burden in patients with mild cognitive impairment.
PMCID: PMC3218803  PMID: 21936965

Results 1-13 (13)