%0 Journal Article %J J Alzheimers Dis %D 2023 %T Microglial Imaging in Alzheimer's Disease and Its Relationship to Brain Amyloid: A Human 18F-GE180 PET Study. %A Yang, Zhengshi %A Banks, Sarah J %A Ritter, Aaron R %A Cummings, Jeffrey L %A Sreenivasan, Karthik %A Kinney, Jefferson W %A Caldwell, Jessica K %A Wong, Christina G %A Miller, Justin B %A Cordes, Dietmar %X

BACKGROUND: Emerging evidence suggests a potential causal role of neuroinflammation in Alzheimer's disease (AD). Using positron emission tomography (PET) to image overexpressed 18 kDA translocator protein (TSPO) by activated microglia has gained increasing interest. The uptake of 18F-GE180 TSPO PET was observed to co-localize with inflammatory markers and have a two-stage association with amyloid PET in mice. Very few studies evaluated the diagnostic power of 18F-GE180 PET in AD population and its interpretation in human remains controversial about whether it is a marker of microglial activation or merely reflects disrupted blood-brain barrier integrity in humans.

OBJECTIVE: The goal of this study was to study human GE180 from the perspective of the previous animal observations.

METHODS: With data from twenty-four participants having 18F-GE180 and 18F-AV45 PET scans, we evaluated the group differences of 18F-GE180 uptake between participants with and without cognitive impairment. An association analysis of 18F-GE180 and 18F-AV45 was then conducted to test if the relationship in humans is consistent with the two-stage association in AD mouse model.

RESULTS: Elevated 18F-GE180 was observed in participants with cognitive impairment compared to those with normal cognition. No regions showed reduced 18F-GE180 uptake. Consistent with mouse model, a two-stage association between 18F-GE180 and 18F-AV45 was observed.

CONCLUSIONS: 18F-GE180 PET imaging showed promising utility in detecting pathological alterations in a symptomatic AD population. Consistent two-stage association between 18F-GE180 and amyloid PET in human and mouse suggested that 18F-GE180 uptake in human might be considerably influenced by microglial activation.

%B J Alzheimers Dis %V 96 %P 1505-1514 %8 2023 Dec 05 %G eng %N 4 %R 10.3233/JAD-230631 %0 Journal Article %J J Alzheimers Dis %D 2019 %T The Pathology of Rapid Cognitive Decline in Clinically Diagnosed Alzheimer's Disease. %A Nance, Christin %A Ritter, Aaron %A Miller, Justin B %A Lapin, Brittany %A Banks, Sarah J %X

BACKGROUND: Variable rate of cognitive decline among individuals with Alzheimer's disease (AD) is an important consideration for disease management, but risk factors for rapid cognitive decline (RCD) are without consensus.

OBJECTIVE: To investigate demographic, clinical, and pathological differences between RCD and normal rates of cognitive decline (NCD) in AD.

METHODS: Neuropsychology test and autopsy data was pulled from the National Alzheimer's Coordinating Center database from individuals with a clinical diagnosis of AD. Individuals with average decline of 3 or more points on the Mini-Mental Status Examination (MMSE) per year over 3 years were labeled RCD; all others were NCD.

RESULTS: Sixty individuals identified as RCD; 230 as NCD. These neuropsychology tests differed at baseline (RCD versus NCD): WMS-LM Immediate Recall (4.35[3.39] versus 6.31[3.97], p < 0.001), Animal Naming (12.1[4.83] versus 13.9[4.83], p = 0.007), TMT Part B (187[86.1] versus 159[79.0], p = 0.02), WAIS-Digit Symbol (29.5[11.3] versus 29.5[11.3], p = 0.04), and the BNT (21.5[7.05] versus 23.6[5.09], p = 0.04). RCD had more thyroid disease (30% versus 16%, p = 0.01) and greater usage of AD medication at baseline (80% versus 62%, p = 0.01). RCD had more severe cerebral amyloid angiopathy (1.62(1.0) versus1.13(1.0), p = 0.002), more neocortical Lewy bodies (20% versus 10%, p = 0.04), and more atrophy (1.54[0.92] versus 1.17[0.83], p = 0.04). A model combining select variables was significant above chance (χ2 = 25.8, p = 0.002), but not to clinical utility (AUC < 0.70; 95% CI).

CONCLUSION: Individuals with RCD have more severe pathology, more comorbidities, and lower baseline neuropsychology test scores of language and executive function.

%B J Alzheimers Dis %V 70 %P 983-993 %8 2019 Aug 20 %G eng %N 4 %R 10.3233/JAD-190302 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Default Mode Network Lateralization and Memory in Healthy Aging and Alzheimer's Disease. %A Banks, Sarah J %A Zhuang, Xiaowei %A Bayram, Ece %A Bird, Chris %A Cordes, Dietmar %A Caldwell, Jessica Z K %A Cummings, Jeffrey L %X

Lateralization of default mode network (DMN) functioning has been shown to change with age. Similarly, lateralization of frontal lobe function has been shown to decline in age. The impact of amyloid pathology and the progression of Alzheimer's disease (AD) on resting state lateralization has not been investigated. Due to the preferential involvement of the left hemisphere in verbal tasks, there may be a benefit to higher levels of left-lateralization in the performance of verbal memory tasks. Here we compared functional lateralization of the anterior and posterior DMN between four groups of participants: amyloid negative (Aβ-) and amyloid positive (Aβ+) groups with normal cognition (NC), and Aβ+ groups with mild cognitive impairment (Aβ+MCI) or dementia (Aβ+AD). Differences were evident between groups in posterior DMN; the Aβ-NC group was more left-lateralized than both cognitively impaired Aβ+ groups. There was no difference in anterior DMN. No differences in overall network connectivity between groups were observed, suggesting that the functional lateralization finding is not secondary to general changes in connectivity. Left-lateralization of both networks was associated with better verbal recall performance. Older subjects, overall, had less left functional lateralization of the anterior DMN.

%B J Alzheimers Dis %V 66 %P 1223-1234 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/30412488?dopt=Abstract %R 10.3233/JAD-180541 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Sex Moderates the Impact of Diagnosis and Amyloid PET Positivity on Hippocampal Subfield Volume. %A Caldwell, Jessica Z K %A Berg, Jody-Lynn %A Shan, Guogen %A Cummings, Jeffrey L %A Banks, Sarah J %X

We examined moderation effects of sex and diagnosis on the effect of positive florbetapir positron emission tomography (PET) amyloid-β (Aβ) scan (A+) on hippocampus subfield volumes in 526 normal control (NC) and early mild cognitive impairment (eMCI) participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI2; ADNI-GO). Regression moderation models showed that women- but not men- with NC designation did not show reduced subiculum volumes despite A+. At the eMCI stage, A+ was detrimental across sexes. Findings were significant while accounting for the effects of age, cognition at screening, education, and APOE4 carrier status. These findings suggest that women with A+ have early neural resistance to Alzheimer's disease-related amyloid burden.

%B J Alzheimers Dis %V 64 %P 79-89 %8 2018 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/29865063?dopt=Abstract %R 10.3233/JAD-180028 %0 Journal Article %J J Alzheimers Dis %D 2017 %T The Association between Montreal Cognitive Assessment Memory Scores and Hippocampal Volume in a Neurodegenerative Disease Sample. %A Ritter, Aaron %A Hawley, Nanako %A Banks, Sarah J %A Miller, Justin B %X

Despite widespread use, there have been few investigations into the neuroanatomical correlates of the Montreal Cognitive Assessment (MoCA). In a sample of 138 consecutive patients presenting with cognitive complaints, we report significant correlations between lower MoCA memory scores and smaller hippocampal volumes (r = 0.36-0.41, p < 0.001). We also report that the newly devised memory index score, designed to better capture encoding deficits than the standard delayed recall score, was not significantly better for predicting hippocampal volume. These initial results suggest that poor performance on the MoCA's memory section should prompt further evaluation for hippocampal atrophy.

%B J Alzheimers Dis %V 58 %P 695-699 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28453481?dopt=Abstract %R 10.3233/JAD-161241