Age, Neuropathology, and Dementia

Savva, George M.; Wharton, Stephen; Ince, Paul G.; Forster, G.; Matthews, Fiona; Brayne, Carol

doi:10.1056/nejmoa0806142

Cited by 801 publications

(648 citation statements)

References 35 publications

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“…A potential limiting factor for tau PET imaging is that Braak staging does not correlate perfectly with clinical symptomatology. In the oldest old NTFs in the hippocampus and neocortical regions are often found in the absence of amyloid deposition [47]. Future studies are needed to determine whether tau PET measurements will be predictive of future cognitive decline in MCI and CN.…”

Section: Tau Imaging Research Findingsmentioning

confidence: 99%

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

et al. 2017

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In vivo imaging of the tau protein has the potential to aid in quantitative diagnosis of Alzheimer's disease, corroborate or dispute the amyloid hypothesis, and demonstrate biomarker engagement in clinical drug trials. A host of tau positron emission tomography agents have been designed, validated, and tested in humans. Several agents have characteristics approaching the ideal imaging tracer with some limitations, primarily regarding off-target binding. Dozens of clinical trials evaluating imaging techniques and several pharmaceutical trials have begun to integrate tau imaging into their protocols.

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Section: Tau Imaging Research Findingsmentioning

confidence: 99%

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

et al. 2017

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“…7 Research has resulted in an increased appreciation of the range of neuropathologies associated with "normal" ageing, which show overlap with pathologies typically associated with neurodegenerative diseases, including brain atrophy, neurofibrillary tangles and amyloid-β plaques. 8 To avoid the confounding influence of 'normal' ageing, many studies investigating TBI-associated neurodegenerative pathologies often exclude older individuals and focus on younger patients. However, the study by Gardner et al 1 underlines the pressing need to further examine the interplay between TBI, age and dementia risk.…”

Section: Age At Injury Influences Dementia Risk After Traumatic Brainmentioning

confidence: 99%

“…8 To avoid the confounding influence of 'normal' ageing, many studies investigating TBI-associated neurodegenerative pathologies often exclude older individuals and focus on younger patients. However, the study by Gardner et al 1 underlines the pressing need to further examine the interplay between TBI, age and dementia risk.…”

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confidence: 99%

Age at injury influences dementia risk after TBI

Johnson

Stewart

2014

Nat Rev Neurol

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Enlighten -Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Several previous clinical studies have used a methodology comparing incidence of dementia in patients with TBI to that of the general population. In the new study by Gardner et al. 1 a more relevant index population of over 112,000 patients exposed to trauma without TBI provides the 'control' population. Over a follow-up period of up to 7 years after the original injury dementia risk in a cohort of almost 52,000 patients with TBI was assessed in comparison to this cohort of Page 3 of 7 patients exposed to trauma without TBI. As such, the authors attempted to mitigate against potentially unknown behavioural or clinical confounders that might also confer an increased risk of dementia in patients exposed to trauma.Rather than relying on self or informant reporting of dementia, only confirmed, hospital-based diagnoses (International Classification of Diseases, NinthRevision coded) were used to determine dementia outcome at follow-up.Importantly, patients in which a diagnosis of dementia was made within 1 year following injury were excluded from the analysis. This criterion reduced the possibility that pre-existing dementia acting as a risk factor for trauma, or evolving subacute TBI pathology might confound dementia diagnosis. Using this methodology, and adjusting for all covariables, the data are reported to show an increased dementia risk in patients surviving TBI compared with patients with trauma, without TBI across all age groups studied.Intriguingly, this study also reveals a potential association between age at injury, injury severity and subsequent risk of dementia. The data demonstrate increased dementia risk following either a moderate, or severe TBI across the cohort.However, in the older patients in this study, defined as those aged e65 at time of injury, just a single, mild TBI was sufficient to increase dementia risk. Notably, TBI is a major public health problem in older individuals, with the highest rates of hospitalization from TBI observed in those aged e65. 7Page 4 of 7Research has resulted in an increased appreciation of the range of neuropathologies associated with "normal" ageing, which show overlap with pathologies typically associated with neurodegenerative diseases, including brain atrophy, neurofibrillary tangles and amyloid-β plaques. 8 To avoid the confounding influence of 'normal' ageing, many studies investigating TBI-associated neurodegenerative pathologies often exclude older individuals and focus on younger patients. However, the study by Gardner et al. 1 underlines the pressing need to further examine the interplay between TBI, age and dementia risk. The presence of comorbidities, and their potential contribution to pathophysiology is of particular relevance in this older age group. In this respect, the population of patients with TBI in this study was slightly older, had a higher percentage of males and a higher incidence of cardiovascular comorbidities than the counterpart cohort of p...

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“…66,67 Indeed, postmortem analyses in elderly individuals have found increased levels of amyloid plaques, but without a diagnosis of AD. 48,72,76 Rather, it is the soluble amyloid peptides that are implicated in AD progression, and these cannot be picked up by either PiB-PET or high-field MRI. (However, there is emerging evidence of the ability to detect increased levels of soluble amyloid peptides in CSF via lumbar puncture several years before AD onset.…”

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confidence: 99%

Seven-Tesla MRI and neuroimaging biomarkers for Alzheimer’s disease

Ali¹,

Goubran

Choudhri³

et al. 2015

FOC

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The goal of this paper was to review the effectiveness of using 7-T MRI to study neuroimaging biomarkers for Alzheimer’s disease (AD). The authors reviewed the literature for articles published to date on the use of 7-T MRI to study AD. Thus far, there are 3 neuroimaging biomarkers for AD that have been studied using 7-T MRI in AD tissue: 1) neuroanatomical atrophy; 2) molecular characterization of hypointensities; and 3) microinfarcts. Seven-Tesla MRI has had mixed results when used to study the 3 aforementioned neuroimaging biomarkers for AD. First, in the detection of neuroanatomical atrophy, 7-T MRI has exciting potential. Historically, noninvasive imaging of neuroanatomical atrophy during AD has been limited by suboptimal resolution. However, now there is compelling evidence that the high resolution of 7-T MRI may help overcome this hurdle. Second, in detecting the characterization of hypointensities, 7-T MRI has had varied success. PET scans will most likely continue to lead in the noninvasive imaging of amyloid plaques; however, there is emerging evidence that 7-T MRI can accurately detect iron deposits within activated microglia, which may help shed light on the role of the immune system in AD pathogenesis. Finally, in the detection of microinfarcts, 7-T MRI may also play a promising role, which may help further elucidate the relationship between cerebrovascular health and AD progression.

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Age, Neuropathology, and Dementia

Abstract: The association between the pathological features of Alzheimer's disease and dementia is stronger in younger old persons than in older old persons. Age must be taken into account when assessing the likely effect of interventions against dementia on the population.

Cited by 801 publications

References 35 publications

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

Age at injury influences dementia risk after TBI

Seven-Tesla MRI and neuroimaging biomarkers for Alzheimer’s disease

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