Parisa Arjmand

The University of Texas MD Anderson Cancer Center

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Licia Luna

Johns Hopkins University

Vivek Yedavalli

Johns Hopkins University

Richard Dagher

Johns Hopkins Medicine

Max Wintermark

Stanford University

Haris I. Sair

Johns Hopkins Medicine

Ali Sheikhy

Tehran University of Medical Sciences

Mahla Radmard

Johns Hopkins University

Daniel A. Stevens

Johns Hopkins University

Mona Gad

Mansoura University

Burak Berksu Ozkara

The University of Texas MD Anderson Cancer Center

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The University of Texas MD Anderson Cancer Center

Johns Hopkins University

Johns Hopkins Medicine

Johns Hopkins Hospital

Mashhad University of Medical Sciences

National Institutes of Health Clinical Center

Mansoura University

University Hospitals of Cleveland

Case Western Reserve University

Stanford University

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Altered Functional Connectivity and Amyloid Deposition in PTSD-Associated Cognitive Impairment

American Journal of Neuroradiology (2025)

Richard Dagher Parisa Arjmand Daniel A. Stevens Max Wintermark Haris I. Sair

ABSTRACT

BACKGROUND AND PURPOSE:

PTSD has been linked to an increased risk of cognitive impairment and dementia, with neuroinflammation, metabolic dysfunction, and neuropathological markers such as beta-amyloid and tau implicated as potential mechanisms. However, the roles of altered functional connectivity and amyloid deposition as biomarkers in the progression of cognitive impairment among PTSD patients remain unclear, with limited and often conflicting evidence from existing neuroimaging studies. This study examines these neuroimaging markers in PTSD patients with and without cognitive impairment to better understand the neurobiological pathways contributing to cognitive decline in PTSD.

MATERIALS AND METHODS:

Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Department of Defense (DOD) ADNI databases. A cohort of 178 age-matched male subjects was divided into four groups: PTSD with cognitive impairment (CI) (PTSD-CI); PTSD and cognitively normal (CN) (PTSD-CN); non-PTSD (NPTSD with CI (NPTSD-CI); and NPTSD and CN (NPTSD-CN). All subjects underwent resting-state functional MRI and amyloid PET imaging, with PTSD diagnosis and CI confirmed through clinical assessments. Functional connectivity was analyzed using the CONN Toolbox, and amyloid burden was quantified via standardized uptake value ratios. Analyses controlled for demographic and genetic factors, including age, education, APOE4 status, and depression.

RESULTS:

Compared to the NPTSD-CN group, the PTSD-CI group showed significantly increased amyloid uptake in the temporal and parietal lobes, with corresponding functional connectivity increase between the bilateral temporal lobes and parietal operculum. In contrast, PTSD-CN patients exhibited no significant amyloid increase but showed increased connectivity between the salience network, postcentral gyri and sensorimotor areas, and decreased connectivity between the sensorimotor network and anterior cingulate cortex. These distinct patterns suggest differing neurobiological profiles between PTSD-CI and PTSD-CN patients.

CONCLUSIONS:

The findings suggest that elevated amyloid and altered connectivity patterns are associated with CI in PTSD, particularly in the temporal and parietal regions. In contrast, PTSD without cognitive decline was associated with functional connectivity changes in salience and sensorimotor networks but no increased amyloid deposition. This study underscores the importance of neuroimaging biomarkers in understanding PTSD-related cognitive decline and suggests avenues for further investigation into the mechanistic pathways involved. ABBREVIATIONS: ACC = anterior division of the cingulate gyrus; ADAS-Cog = Alzheimer's Disease Assessment Scale-Cognitive; CAPS = Clinician-Administered PTSD Scale; PTSD = post-traumatic stress disorder; CI = cognitively impaired; CN = cognitively normal; ECog = Everyday Cognition; GDS = Geriatric Depression Scale; MoCA = Montreal Cognitive Assessment; NPTSD = non-PTSD.

Amyloid (mycology)

10.3174/ajnr.a8694

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Diagnostic Performance of ASL-MRI and FDG-PET in Frontotemporal Dementia: A Systematic Review and Meta-Analysis

American Journal of Neuroradiology (2024)

Richard Dagher Parisa Arjmand Burak Berksu Ozkara Mahla Radmard Mona Gad

While the diagnosis of frontotemporal dementia (FTD) is based mostly on clinical features, [18F]-FDG-PET has been investigated as a potential imaging standard in ambiguous cases, with arterial spin-labeling (ASL) MRI gaining recent interest. The purpose of this study is to conduct a systematic review and meta-analysis on the diagnostic performance of ASL MRI in patients with FTD and compare it with that of [18F]-FDG-PET. A systematic search of PubMed, Scopus, and Embase was conducted until March 13, 2024. Inclusion criteria were original articles, patients with FTD and/or its variants, use of ASL MR perfusion imaging with or without [18F]-FDG-PET, and presence of sufficient diagnostic performance data. Exclusion criteria were meeting abstracts, comments, summaries, protocols, letters and guidelines, longitudinal studies, and overlapping cohorts. The quality of eligible studies was assessed by using the Quality Assessment of Diagnostic Accuracy Studies-2. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) for [18F]-FDG-PET and ASL MRI were calculated, and a summary receiver operating characteristic curve was plotted. Seven eligible studies were identified, which included a total of 102 patients with FTD. Aside from some of the studies showing, at worst, an unclear risk of bias in patient selection, index test, flow, and timing, all studies showed low risk of bias and applicability concerns in all categories. Data from 4 studies were included in our meta-analysis for ASL MRI and 3 studies for [18F]-FDG-PET. Pooled sensitivity, specificity, and DOR were 0.70 (95% CI: 0.59-0.79), 0.81 (95% CI: 0.71-0.88), and 8.00 (95% CI: 3.74-17.13) for ASL MRI and 0.88 (95% CI: 0.71-0.96), 0.89 (95% CI: 0.43-0.99), and 47.18 (95% CI: 10.77-206.75) for [18F]-FDG-PET. The number of studies was relatively small, with a small sample size. The studies used different scanning protocols as well as a mix of diagnostic metrics, all of which might have introduced heterogeneity in the data. While ASL MRI performed worse than [18F]-FDG-PET in the diagnosis of FTD, it exhibited a decent diagnostic performance to justify its further investigation as a quicker and more convenient alternative.

10.3174/ajnr.a8440

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