Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly

Aizenstein, Howard J.; Nebes, Robert D.; Saxton, Judith; Price, Julie C.; Mathis, Chester A.; Tsopelas, Nicholas D.; Ziolko, Scott K.; James, Jeffrey A.; Snitz, Beth E.; Houck, Patricia R.; Bi, Wenzhu; Cohen, Ann D.; Lopresti, Brian J.; DeKosky, Steven T.; Halligan, Edythe M.; Klunk, William E.

doi:10.1001/archneur.65.11.1509

Cited by 927 publications

(797 citation statements)

References 47 publications

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“…As reviewed recently, 18,36 20% to 40% of healthy elderly 460 years of age (and up to 50% above 80) have a significant amyloid burden on PET imaging, despite normal general cognition. 37 Our prevalence of 44% is therefore high but consistent with these ranges. It is also consistent with the CAA study of Johnson et al, 6 where 6/15 (40%) of their HAMCs were PiB þ .…”

Section: Discussionsupporting

confidence: 85%

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Baron

Farid

Dolan

et al. 2014

J Cereb Blood Flow Metab

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By detecting β-amyloid ( Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (I-ICH). No previous study has directly assessed the diagnostic value of 11-Pittsburgh compound B (PiB) PET in probable CAA-related I-ICH against healthy controls (HCs). 11C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic I-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity = 91%, specificity = 55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, 11C-PiB-PET has low specificity for CAA due to the frequent occurrence of high 11C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials.

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Section: Discussionsupporting

confidence: 85%

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Baron

Farid

Dolan

et al. 2014

J Cereb Blood Flow Metab

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“…However, it is insufficient for Ab plaques and hyperphosphorylated tau to explain all the features of AD. In 2008, a study discovered that significant burden of Ab deposition found in elderly persons did not necessarily cause clinically cognitive impairments (Aizenstein et al 2008). Moreover, clinically reduced Ab in the brain through immune-therapeutics did not improve the AD patients' cognitive functions (Holmes et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Zhang

et al. 2015

Arch. Immunol. Ther. Exp.

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Alzheimer's disease (AD) is a complex agerelated neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease. After three decades of genetic study in AD, dozens of loci harboring genetic variants influencing inflammatory pathways in AD patients has been identified through genome-wide association studies (GWAS). The most well-known GWAS risk factor that is responsible for immune response and inflammation in AD development should be APOE e4 allele. However, a growing number of other GWAS risk AD candidate genes in inflammation have recently been discovered. In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.

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“…Basal ganglia may shrink by the age per se [49], or because of the disruption of their connections with the cerebral cortex caused by WMH and/or lacunae, or as a consequence of the age-related cortical thinning [50]. Although only speculative, given that a nonnegligible percentage of cognitively unimpaired elderly-old subjects have an increased Ab deposition [5][6][7][8], an additional contribution to subcortical atrophy could be caused by the retrograde transport of Ab along axonal membranes [51] to basal ganglia cell bodies. Interestingly, Ab deposition [52] and atrophy [53] have been described in the striatum of different Alzheimer disease (AD) mutation carriers and sporadic AD [54,55].…”

Section: Discussionmentioning

confidence: 99%

“…Evidences of amyloid b (Ab) deposition and cerebrovascular pathology have been demonstrated at postmortem examinations of the brain of non-demented individuals [4]. Results from Ab PET studies show that about 20-40 % of cognitively unimpaired subjects aged 60-90 years have high levels of Ab deposition [5,6] and faster rates of cortical atrophy than those with low Ab deposition [7]. Furthermore, 54 % of cognitively normal subjects aged 50-89 years present a various combination of imaging biomarkers of b-amyloidosis and neurodegeneration [8].…”

Section: Introductionmentioning

confidence: 99%

Isolated, subtle, neurological abnormalities in neurologically and cognitively healthy aging subjects

et al. 2015

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The aim of this study is to describe the frequency of isolated, subtle, neurological abnormalities (ISNAs) in a large population of neurologically and cognitively healthy subjects and to compare ISNAs to various types of MRI-detected cerebrovascular lesions and subcortical brain atrophy in different age classes. 907 subjects were selected from a large, prospective hospital-based study. At baseline neurological examination, 17 ISNAs were selected. Primitive reflexes were the most common ISNAs (35.8 %), while dysphagia was the most rarely encountered (0.3 %). Measures of small vessel disease, i.e., deep and subcortical white matter hyperintensity and lacunar infarcts as well as subcortical atrophy, were variously associated with ISNAs. In the adult group, the ISNAs were associated with hypertriglyceridemia, TIA, and subcortical lacunar infarcts, while in the elderly-old group they were associated with arterial hypertension, subcortical white matter hyperintensity, and subcortical atrophy. An increased risk of ISNAs was associated with lacunae and white matter hyperintensity in the parietal region. This study shows that white matter hyperintensity, lacunae, and subcortical atrophy are associated with an increased risk of ISNAs in cognitively and neurologically healthy aging subjects. ISNAs are not benign signs. Therefore, adults and elderly people presenting with ISNAs should have access to accurate history and diagnosis to prevent progression of small vessel disease and future neurological and cognitive disabilities.

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Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly

Cited by 927 publications

References 47 publications

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Isolated, subtle, neurological abnormalities in neurologically and cognitively healthy aging subjects

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