Abstract Context Perceived cognitive impairment (PCI) has been shown to be one of the most common symptoms after breast cancer treatment. However, this symptom does not always correlate with ...objective cognitive performance and is often highly associated with other patient-reported symptoms. Objectives Using a sample of breast cancer survivors (BCS), this study examined relationships among the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) scale, a self-report questionnaire that measures PCI; impact on quality of life (QoL); comments from others (other); perceived cognitive ability (PCA); objective cognitive performance on tests of verbal memory, speed of processing, and executive functioning; and other symptoms (fatigue, depression, anxiety, and sleep disturbance). Methods The BCS who were aged 40 years or older and at least one year post-chemotherapy treatment were enrolled. Participants completed questionnaires and a brief neuropsychological assessment. Results A total of 88 BCS who were on average 56.7 (SD 8.5) years old and 5.3 (SD 4.1) years post-treatment participated; 94% reported clinically significant PCI. The PCI was significantly correlated with some objective measures of immediate and delayed verbal memory and executive function, whereas PCA was associated with all these measures. The PCI and PCA were both significantly associated with depressive symptoms, fatigue, and anxiety, but only PCI was related to poor global sleep quality. Conclusion The PCA was highly correlated with objective neuropsychological performance and may be clinically useful in identifying problems with verbal memory and executive functioning in BCS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina.
To ...investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline.
75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant.
Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes.
RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.
Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of ...longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.
This study aimed to determine the pattern of
Fflortaucipir uptake in individuals affected by Gerstmann-Sträussler-Scheinker disease (GSS) associated with the PRNP F198S mutation. The aims were to: ...1) determine the pattern of
Fflortaucipir uptake in two GSS patients; 2) compare tau distribution by
Fflortaucipir PET imaging among three groups: two GSS patients, two early onset Alzheimer's disease patients (EOAD), two cognitively normal older adults (CN); 3) validate the PET imaging by comparing the pattern of
Fflortaucipir uptake, in vivo, with that of tau neuropathology, post-mortem. Scans were processed to generate standardized uptake value ratio (SUVR) images. Regional
Fflortaucipir SUVR was extracted and compared between GSS patients, EOADs, and CNs. Neuropathology and tau immunohistochemistry were carried out post-mortem on a GSS patient who died 9 months after the
Fflortaucipir scan. The GSS patients were at different stages of disease progression. Patient A was mildly to moderately affected, suffering from cognitive, psychiatric, and ataxia symptoms. Patient B was moderately to severely affected, suffering from ataxia and parkinsonism accompanied by psychiatric and cognitive symptoms. The
Fflortaucipir scans showed uptake in frontal, cingulate, and insular cortices, as well as in the striatum and thalamus. Uptake was greater in Patient B than in Patient A. Both GSS patients showed greater uptake in the striatum and thalamus than the EOADs and greater uptake in all evaluated regions than the CNs. Thioflavin S fluorescence and immunohistochemistry revealed that the anatomical distribution of tau pathology is consistent with that of
Fflortaucipir uptake. In GSS patients, the neuroanatomical localization of pathologic tau, as detected by
Fflortaucipir, suggests correlation with the psychiatric, motor, and cognitive symptoms. The topography of uptake in PRNP F198S GSS is strikingly different from that seen in AD. Further studies of the sensitivity, specificity, and anatomical patterns of tau PET in diseases with tau pathology are warranted.
Abstract
Visual deficits are common in neurodegenerative diseases including Alzheimer’s disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures ...of Alzheimer’s disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer’s disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer’s disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with 18Fflortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer’s disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer’s disease-related pathology in older adults at risk for cognitive decline.
Poorer visual contrast sensitivity was associated with greater cerebral amyloid and tau in individuals with or at risk for Alzheimer’s disease. Visual contrast sensitivity accurately predicted the presence of cerebral amyloid or tau. Visual contrast sensitivity has potential as a non-invasive screening tool to detect Alzheimer’s pathophysiology in at-risk individuals.
Graphical Abstract
Graphical Abstract
We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration.
Thirty-four older adults, including 19 cognitively ...normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD.
Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT.
Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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