Publications by authors named "Danielle Goldfarb"

9 Publications

  • Page 1 of 1

The relationship between cerebral and retinal microbleeds in cerebral amyloid angiopathy (CAA): A pilot study.

J Neurol Sci 2021 04 1;423:117383. Epub 2021 Mar 1.

Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA; George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA; Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA; Department of Surgery (Ophthalmology), Alpert Medical School of Brown University, Providence, RI, USA.

Background: The standard in vivo diagnostic imaging technique for cerebral amyloid angiopathy (CAA) is costly and thereby of limited utility for point-of-care diagnosis and monitoring of treatment efficacy. Recent recognition that retinal changes may reflect cerebral changes in neurodegenerative disease provides an ideal opportunity for development of accessible and cost-effective biomarkers for point-of-care use in the detection and monitoring of CAA. In this pilot study, we examined structural and angiographic retinal changes in CAA patients relative to a control group, and compared retinal and cerebral pathology in a group of CAA patients.

Methods: We used spectral domain optical coherence tomography (SD-OCT) to image the retina and compared retinal microbleeds to both cerebral microbleeds and white matter hyperintensities (WMH) in CAA patients, as seen on MRI. We compared retinal angiographic changes, along with structural retinal neuronal layer changes in CAA patients and cognitively normal older adults, and examined the relationship between retinal and cerebral microbleeds and cognition in CAA patients.

Results: We found a trend level correlation between retinal and cerebral microbleeds in CAA patients. Moreover, we found a significant correlation between retinal microbleeds and episodic memory performance in CAA patients. There were no significant group differences between CAA patients and cognitively normal older adults on retinal angiographic or structural measurements.

Conclusion: Retinal microbleeds may reflect degree of cerebral microbleed burden in CAA. This picture was complicated by systolic hypertension in the CAA group, which is a confounding factor for the interpretation of these data. Our results stimulate motivation for pursuit of a more comprehensive prospective study to determine the feasibility of retinal biomarkers in CAA.
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http://dx.doi.org/10.1016/j.jns.2021.117383DOI Listing
April 2021

Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease.

medRxiv 2021 Feb 18. Epub 2021 Feb 18.

The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus, leptomeninges, median eminence of the hypothalamus and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction and one with hemorrhagic encephalitis, that was unequivocally related to their COVID-19 disease while most of the 18 other subjects had non-specific histopathology including focal β-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.
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http://dx.doi.org/10.1101/2021.02.15.21251511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899461PMC
February 2021

Disruption of cholinergic neurotransmission, within a cognitive challenge paradigm, is indicative of Aβ-related cognitive impairment in preclinical Alzheimer's disease after a 27-month delay interval.

Alzheimers Res Ther 2020 03 24;12(1):31. Epub 2020 Mar 24.

Department of Biological & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 75 Lower College Road, 2nd Floor, Kingston, RI, USA.

Background: Abnormal beta-amyloid (Aβ) is associated with deleterious changes in central cholinergic tone in the very early stages of Alzheimer's disease (AD), which may be unmasked by a cholinergic antagonist (J Prev Alzheimers Dis 1:1-4, 2017). Previously, we established the scopolamine challenge test (SCT) as a "cognitive stress test" screening measure to identify individuals at risk for AD (Alzheimer's & Dementia 10(2):262-7, 2014) (Neurobiol. Aging 36(10):2709-15, 2015). Here we aim to demonstrate the potential of the SCT as an indicator of cognitive change and neocortical amyloid aggregation after a 27-month follow-up interval.

Methods: Older adults (N = 63, aged 55-75 years) with self-reported memory difficulties and first-degree family history of AD completed the SCT and PET amyloid imaging at baseline and were then seen for cognitive testing at 9, 18, and 27 months post-baseline. Repeat PET amyloid imaging was completed at the time of the 27-month exam.

Results: Significant differences in both cognitive performance and in Aβ neocortical burden were observed between participants who either failed vs. passed the SCT at baseline, after a 27-month follow-up period.

Conclusions: Cognitive response to the SCT (Alzheimer's & Dementia 10(2):262-7, 2014) at baseline is related to cognitive change and PET amyloid imaging results, over the course of 27 months, in preclinical AD. The SCT may be a clinically useful screening tool to identify individuals who are more likely to both have positive evidence of amyloidosis on PET imaging and to show measurable cognitive decline over several years.
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http://dx.doi.org/10.1186/s13195-020-00599-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093953PMC
March 2020

Developing retinal biomarkers for the earliest stages of Alzheimer's disease: What we know, what we don't, and how to move forward.

Alzheimers Dement 2020 01;16(1):229-243

Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, USA.

The last decade has seen a substantial increase in research focused on the identification, development, and validation of diagnostic and prognostic retinal biomarkers for Alzheimer's disease (AD). Sensitive retinal biomarkers may be advantageous because they are cost and time efficient, non-invasive, and present a minimal degree of patient risk and a high degree of accessibility. Much of the work in this area thus far has focused on distinguishing between symptomatic AD and/or mild cognitive impairment (MCI) and cognitively normal older adults. Minimal work has been done on the detection of preclinical AD, the earliest stage of AD pathogenesis characterized by the accumulation of cerebral amyloid absent clinical symptoms of MCI or dementia. The following review examines retinal structural changes, proteinopathies, and vascular alterations that have been proposed as potential AD biomarkers, with a focus on studies examining the earliest stages of disease pathogenesis. In addition, we present recommendations for future research to move beyond the discovery phase and toward validation of AD risk biomarkers that could potentially be used as a first step in a multistep screening process for AD risk detection.
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http://dx.doi.org/10.1002/alz.12006DOI Listing
January 2020

Current and Emerging Solutions to Challenges in the Management of Alzheimer's Disease.

J Clin Psychiatry 2019 12 3;80(6). Epub 2019 Dec 3.

Beth Israel-Deaconess Hospital, Boston, Massachusetts, USA.

​​​​Effective multifactorial management of Alzheimer's disease (AD) requires a triadic alliance of the clinician, the patient, and the patient's family and/or care partner(s). During the evaluation process and when the diagnosis of AD is delivered, these parties must work together to set goals and develop care plans. Care plans should be designed to help the patient maintain safety and autonomy as long as he or she can and, once autonomy is no longer possible, to allow the patient and care partner(s) to experience as much comfort and the best possible quality of life for as long as possible. In this Academic Highlights, faculty members from neurology, psychiatry, neuropsychology, and primary care share their recommendations, supported by current evidence and guidelines, for handling the complexities of providing care for patients with AD.
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http://dx.doi.org/10.4088/JCP.MS18002AH3CDOI Listing
December 2019

A Multidisciplinary Approach for Addressing Challenges in Alzheimer's Disease.

J Clin Psychiatry 2019 09 24;80(5). Epub 2019 Sep 24.

Banner Alzheimer's Institute, Phoenix, Arizona, USA.

In this webcast, experts from the Banner health care system discuss the evaluation of cognitive concerns and cognitive impairment, and the diagnosis and management of Alzheimer's disease (AD). Topics of the brief video clips include methods for developing therapeutic rapport with patients and their families, identifying and assessing the patient's and/or the care partner's concern, detecting cognitive impairment, characterizing the patient's cognitive-behavioral syndrome, and investigating and determining the etiology of the cognitive impairment or dementia syndrome. The experts also address strategies for delivering a diagnosis to patients and their care partners, planning treatment regimens, and offering education and support. Task-sharing and collaboration must occur between specialists and primary care clinicians to address the growing number of individuals with AD and related dementias.
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http://dx.doi.org/10.4088/JCP.MS18002WC4CDOI Listing
September 2019

Diagnosing and Treating Depression in Patients with Alzheimer's Disease.

Neurol Ther 2019 Dec 21;8(2):325-350. Epub 2019 Aug 21.

Wellspan Philhaven, Mount Gretna, PA, USA.

Although cognitive and functional impairment are the hallmark features of Alzheimer's disease (AD), neuropsychiatric symptoms associated with AD account for increased rates of disability and profoundly impact the quality of life of both patients and their caregivers. This narrative review of current evidence provides practical guidance in diagnosing and managing depression in patients with AD using pharmacological and nonpharmacological interventions. After apathy, depression is the second most common neuropsychiatric symptom in AD. Diagnosing late-life depression (LLD), particularly in those affected by AD, is complicated because older patients may not meet the criteria for a major depressive disorder. Clinically, late-life depression and dementia can be indistinguishable. Although these two entities are now thought to be related, the pathologic mechanisms remain unclear. Evidence suggests that LLD may be a prodromal symptom of neurodegenerative disease. The various geropsychiatric measures currently used to diagnose, rate the severity of, and monitor the progress of treatment for depression are imperfect. Neuroimaging represents a promising avenue toward understanding the complex pathophysiologic relationships between dementia and LLD, and will support the pursuit of biomarker-driven diagnosis and treatment. Nonpharmacologic interventions to relieve depression in persons with cognitive impairment and dementia include emotion-oriented therapies, behavioral and cognitive-behavioral modification programs, and structured activity programs. Sensory-stimulation therapies and multisensory approaches show some promise for successfully treating depression in patients with dementia, but further rigorous research is needed to establish their validity. Clinical consensus and research appear to support selective serotonin reuptake inhibitors as a first choice for the pharmacological treatment of depression in patients with dementia. However, initial support for these therapies remains variable, and further investigation is needed. Extra care is required in prescribing to this population because of the generally high level of medical and psychiatric comorbidity and the potential difficulty in assessing the cognitively impaired patient's response.
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http://dx.doi.org/10.1007/s40120-019-00148-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858899PMC
December 2019

Cognitive Assessment of Alzheimer's Disease and Dementias in Clinical Practice: Pragmatics of Brief Instruments and Neuropsychological Evaluation.

J Clin Psychiatry 2019 06 25;80(4). Epub 2019 Jun 25.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Detection of cognitive impairment and dementia (CID) through the use of brief cognitive assessment tools (BCATs) is the first step to establishing an accurate diagnosis and care plan for individuals seen in primary practices. While the cognitive-behavioral syndrome and underlying etiology may not be readily apparent through brief assessment, clinicians can refer patients for a more comprehensive neuropsychological evaluation. A timely diagnosis maximizes the potential for patients to be involved in decision-making and planning for their future, and allows for expedited intervention and harm reduction. This activity provides a practical review of validated and standardized BCATs that can aid in the detection of CID; reviews cognitive and neuropsychological domains and their clinical relevance; and delineates circumstances for referral to neuropsychology and the utility of neuropsychological evaluation to practicing clinicians.
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http://dx.doi.org/10.4088/JCP.MS18002BR2CDOI Listing
June 2019

Disclosure of Alzheimer's Disease and Dementia: Patient- and Care Partner-Centric Decision-Making and Communication.

J Clin Psychiatry 2019 03 19;80(2). Epub 2019 Mar 19.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Disclosing the diagnosis of cognitive impairment or dementia due to Alzheimer's disease (AD) and Related Dementias (ADRD) can be one of the most challenging aspects of dementia care for clinicians. However difficult the diagnosis is to give or receive, evidence and evidence-based consensus support that disclosing a timely AD/ADRD diagnosis, accompanied by psychoeducation and care planning, is beneficial to patient-care partner dyads. Diagnosis, provided as early as possible, increases the likelihood for patients to be involved in decision-making and planning for their future and allows care options to be implemented sooner to provide greater clinical and quality-of-life benefits, reduce potential for harm, and mitigate symptoms and decline. Using patient-centered communication and following a structured process, clinicians can provide a successful disclosure of diagnosis as a component of the necessary foundation to implement impactful management and care planning for patients and caregivers going through a life-changing process.
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http://dx.doi.org/10.4088/JCP.MS18002BR1CDOI Listing
March 2019