Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study

Burnham, Samantha; Bourgeat, Pierrick; Doré, Vincent; Savage, Greg; Brown, Belinda M.; Laws, Simon M.; Maruff, Paul; Salvado, Olivier; Ames, David; Martins, Ralph N.; Masters, Colin L.; Rowe, Christopher C.; Villemagne, Victor L.

doi:10.1016/s1474-4422(16)30125-9

Cited by 183 publications

(183 citation statements)

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“…46 ADT may not have a direct causative relationship with AD, however, the initiation of ADT and related side effects may create a favorable environment for a slow, and ongoing disease process of AD to progress at a more rapid pace. 47 …”

Section: Discussionmentioning

confidence: 99%

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

Cherrier

Cross

Higano

et al. 2018

Prostate Cancer Prostatic Dis

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ObjectiveAndrogen deprivation therapy (ADT) is a common treatment option for men with biochemical relapse from prostate cancer. ADT is associated with changes in mood, cognition, and quality of life, and most recently with increased risk for Alzheimer’s disease (AD). This study examined changes in brain metabolism using positron emission tomography (PET) in men undergoing intermittent ADT.MethodsNine men with prostate cancer and a rising PSA (biochemical recurrence) without evidence of metastases were treated with intermittent ADT consisting of 9 months of complete androgen blockade achieved with combined leuprolide acetate and flutamide. Patients underwent resting [Fuorine-18] fluorodeoxyglucose PET (18F-FDGPET) at baseline (before treatment) and again after 9 months of ADT.ResultsWhole-brain mapping analysis after 9 months of androgen deprivation compared to pretreatment baseline revealed decreased regional cerebral glucose metabolism in the cerebellum, posterior cingulate, and medial thalamus bilaterally. Associations of brain metabolism with measurements of cognition and mood while on androgen deprivation revealed positive correlations between the posterior cingulate, left inferior parietal lobule (BA40), and left mid temporal gyrus (BA39) and spatial reasoning and a negative correlation between left inferior parietal lobule and verbal memory. Several mood indices were negatively correlated with hypothalamus and brainstem.ConclusionThese findings suggest that complete androgen deprivation may result in changes in regional brain metabolism associated with variation in mood, verbal memory, and spatial performance. Brain regions that were impacted from ADT are similar and overlap with brain regions with metabolic decline found in early AD and diabetes, suggesting possible common mechanisms.

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Section: Discussionmentioning

confidence: 99%

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

Cherrier

Cross

Higano

et al. 2018

Prostate Cancer Prostatic Dis

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“…To reflect NIA-AA staging while accounting for SNAP and AN− groups, many research groups have adopted a 2-class biomarker construct in which individuals are assigned to one of four biomarker categories: A− N−, A+N−, A− N+ (SNAP) or A+N+. 8-13 This approach has been useful because it provided a common framework for different research groups to communicate findings in their own cohorts. 14-18 …”

Section: Introductionmentioning

confidence: 99%

Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50–95 years: a cross-sectional study

Jack

Wiste

Weigand

et al. 2017

The Lancet Neurology

260

236

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SummaryBackgroundA new descriptive classification scheme for biomarkers used in Alzheimer's and cognitive aging research, labeled ATN, was recently proposed. One implementation of this ATN construct dichotomizes biomarkers of amyloid, tau, and neurodegeneration/neuronal injury as normal or abnormal resulting in 2 × 2× 2=8 possible biomarker profiles. We determined the clinical characteristics and prevalence of each ATN group among clinically normal individuals aged 50 and older from a population based cohort.MethodsAll individuals in this study were participants in the Mayo Clinic Study of Aging, a population-based study of cognitive aging. Potential participants were randomly selected from the Olmsted County, Minnesota population by age- and sex-stratification and invited to participate in cognitive evaluations and undergo multimodality imaging. To be eligible for inclusion in this study, participants must have been judged clinically to have no cognitive impairment and have undergone multi-modality imaging. Imaging studies were obtained from October 11, 2006 to October 5, 2016. All participants were classified as having normal (A−) or abnormal (A+) amyloid using amyloid PET, normal (T−) or abnormal (T+) tau using tau PET, and normal (−) or abnormal (N+) neurodegeneration/neuronal injury using cortical thickness. The cut points used were SUVR 1·42 (centiloid 19) for amyloid PET, 1·23 SUVR for tau PET, and 2·67 mm for MRI cortical thickness. Age- and sex- specific prevalences of the eight ATN biomarker groups were determined using 435 individuals with amyloid PET, tau PET, and MR imaging and 1113 additional clinically normal individuals who underwent amyloid PET and MR imaging, but not tau PET imaging.FindingsThere were 165 A−T−N-, 35 A−T+N-, 63 A−T−N+, 19 A−T+N+, 44 A+T−N−, 25 A+T+N−, 35 A+T−N+, and 49 A+T+N+ individuals. Age differed by ATN group (p<0 001) ranging from a median age of 57 in the A−T−N-−and A−T+N− groups to 80 in the A+T−N+ and A+T+N+ groups. The frequency of APOE ε4 carriers differed by ATN group (p=0·04) with ε4 carriers roughly twice as frequent in A+ versus A−. White matter hyperintensity volume (p<0·0001), and cognitive performance (p<0·0001) also differed by ATN group. Tau PET and neurodegeneration biomarkers were discordant in the majority of individuals who would be labeled stage 2/3 preclinical AD (86% at age 65 and 51% at age 80) or suspected non-Alzheimer's pathophysiology (SNAP) (92% at age 65 and 78% at age 80). From age 50, A−T−N− prevalence declines while A+T+N+ and A−T+N+ increase continuously with age. In both men and women, A−T−N− is the most prevalent group until their late 70s. After about age 80, A+T+N+ is the most prevalent group until their late 70s. After about age 80, A+T+N+ is the most prevalent group. The remaining ATN groups reach individual peaks in the 60–90 age range and then decline in prevalence. By age 85 over 90% of men and women have one or more biomarker abnormalities.InterpretationBiomarkers of fibrillar tau deposition can be included with those of Aβ and neur...

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“…Most of these biomarkers have been validated in populations of symptomatic patients and are associated with high sensitivity and specificity for mild cognitive impairment (MCI) and AD dementia [9]. While several longitudinal follow-up studies have examined the potential role of AD neuroimaging biomarkers to predict subsequent decline in cognition among cognitively normal subjects [12–19], very few have examined the predictive value of combined CSF and neuroimaging biomarkers in this population; something that may prove key to accurately identifying candidates who could benefit most from therapies aimed at preserving cognition in the presence of brain AD pathology.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Disease Biomarkers and Future Decline in Cognitive Normal Older Adults

Dumurgier

Hanseeuw

Hatling

et al. 2017

JAD

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Background Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer’s disease (AD) modifying therapies move towards preclinical stages. Objective To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults. Methods 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer’s Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of beta-amyloid 1-42 (Ab42), total Tau (t-Tau) and Tau phosphorylated at threonine 181 (p-Tau181) in the CSF at study entry were available in all cases. Baseline brain MRI, FDG-PET and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models. Results 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score. Conclusions Baseline CSF t-Tau and p-Tau181, in vivo amyloid load and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

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Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study

Cited by 183 publications

References 31 publications

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

Changes in cerebral metabolic activity in men undergoing androgen deprivation therapy for non-metastatic prostate cancer

Age-specific and sex-specific prevalence of cerebral β-amyloidosis, tauopathy, and neurodegeneration in cognitively unimpaired individuals aged 50–95 years: a cross-sectional study

Alzheimer’s Disease Biomarkers and Future Decline in Cognitive Normal Older Adults

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