<scp>NIA‐AA</scp> Alzheimer's Disease Framework: Clinical Characterization of Stages

Petersen, Ronald C.; Wiste, Heather J.; Weigand, Stephen D.; Fields, Julie A.; Geda, Yonas E.; Graff‐Radford, Jonathan; Knopman, David S.; Kremers, Walter K.; Lowe, Val J.; Machulda, Mary M.; Mielke, Michelle M.; Stricker, Nikki H.; Therneau, Terry M.; Vemuri, Prashanthi; Jack, Clifford R.

doi:10.1002/ana.26071

Cited by 38 publications

(31 citation statements)

References 39 publications

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“…Pearson's correlations were used to assess the association between 3-month slopes on the C3 and change on the PACC5 over 1 year. We then conducted Receiver Operating Characteristic (ROC) analyses to quantify how accurately C3 slopes could identify individuals who would show more than 0.10 SD decline on the PACC5 over 1 year, which has previously been suggested as a clinically meaningful cut-off for annual decline in amyloid positive cognitively normal individuals (Papp et al, 2020 ; Petersen et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Upon seeing improvement, we investigated whether PE on computerized testing could be observed over the first 3 months, as we expected that the PE signal would be strongest over the first 4–5 assessments (Watson et al, 1994 ; Calamia et al, 2012 ; Samaroo et al, 2020 ). Next, we examined the relationship of individual variation in shorter term PE (i.e., 3 months) with (1) AD biomarker burden measured using neuroimaging and (2) cognitive decline on standard paper-pencil cognitive testing over 1 year (Petersen et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

Jutten

Rentz

et al. 2022

Front. Aging Neurosci.

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Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline.Materials and Methods:N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed >0.10 SD annual decline on the PACC-5.Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p < 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p < 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = −0.38, 95% CI [−0.54 – −0.19], p < 0.001) and inferior-temporal lobe (r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 (p < 0.001) and baseline PACC-5 scores (p = 0.02).Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

Jutten

Rentz

et al. 2022

Front. Aging Neurosci.

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“…However, from the two studies that did include younger adult individuals (age ≥ 30), both found significant associations between MeDi and structural (specifically WMI) and functional neuroimaging markers (specifically Aβ and glucose metabolism) ( 34 , 39 ). It has been suggested that the earliest pathological changes may be detected using neuroimaging markers between 15 and 30 years preceding symptom onset ( 42 , 73 , 74 ). As most studies captured older-aged individuals, it is difficult to understand how long an individual must have adhered to a DP, to influence changes in brain ageing.…”

Section: Discussionmentioning

confidence: 99%

Associations Between Dietary Patterns and Neuroimaging Markers: A Systematic Review

et al. 2022

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Dementia is a complex, growing challenge for population health worldwide. Dietary patterns (DPs) may offer an opportunity to beneficially influence cognitive ageing and potentially reduce an individuals’ risk of dementia through diet-related mechanisms. However, previous studies within this area have shown mixed results, which may be partly explained by the lack of sensitivity and accuracy within cognitive testing methods. Novel neuroimaging techniques provide a sensitive method to analyse brain changes preceding cognitive impairment which may have previously remained undetected. The purpose of this systematic review was to elucidate the role of DPs in relation to brain ageing processes, by summarising current prospective and intervention studies. Nine prospective studies met the inclusion criteria for the review, seven evaluated the Mediterranean diet (MeDi), one evaluated the Alternative Healthy Eating Index-2010, and one evaluated a posteriori derived DPs. No intervention studies were eligible for inclusion in this review. There was some evidence of an association between healthy DPs and neuroimaging markers including changes within these markers over time. Consequently, it is plausible that better adherence to such DPs may positively influence brain ageing and neurodegeneration. Future studies may benefit from the use of multi-modal neuroimaging techniques, to further investigate how adherence to a DP influences brain health. The review also highlights the crucial need for further intervention studies within this research area.

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“…74 However, the true application of these new research-based criteria needs validation and is likely to undergo further revisions. 75 Positron Emission Tomography-based Biomarkers Currently four tracers for Aβ plaques and neurofibrillary tau have been approved by the US Food and Drug Administration (FDA). For both Aβ and tau pathologies, postmortem studies have demonstrated a strong regional correlation between premortem PET scans and postmortem pathology.…”

Section: Pathology-related Biomarkersmentioning

confidence: 99%

Alzheimer Disease

McDade¹

2022

CONTINUUM: Lifelong Learning in Neurology

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PURPOSE OF REVIEWAlzheimer disease (AD) is the most common cause of dementia in adults (mid to late life), highlighting the importance of understanding the risk factors, clinical manifestations, and recent developments in diagnostic testing and therapeutics.RECENT FINDINGSAdvances in fluid (CSF and blood-based) and imaging biomarkers are allowing for a more precise and earlier diagnosis of AD (relative to non-AD dementias) across the disease spectrum and in patients with atypical clinical features. Specifically, tau- and amyloid-related AD pathologic changes can now be measured by CSF, plasma, and positron emission tomography (PET) with good precision. Additionally, a better understanding of risk factors for AD has highlighted the need for clinicians to address comorbidities to maximize prevention of cognitive decline in those at risk or to slow decline in patients who are symptomatic. Recent clinical trials of amyloid-lowering drugs have provided not only some optimism that amyloid reduction or prevention may be beneficial but also a recognition that addressing additional targets will be necessary for significant disease modification.SUMMARYRecent developments in fluid and imaging biomarkers have led to the improved understanding of AD as a chronic condition with a protracted presymptomatic phase followed by the clinical stage traditionally recognized by neurologists. As clinical trials of potential disease-modifying therapies continue, important developments in the understanding of the disease will improve clinical care now and lead to more effective therapies in the near future.

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NIA‐AA Alzheimer's Disease Framework: Clinical Characterization of Stages

Cited by 38 publications

References 39 publications

Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

Associations Between Dietary Patterns and Neuroimaging Markers: A Systematic Review

Alzheimer Disease

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