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

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

Diagnosing and Treating Depression in Patients with Alzheimer’s Disease

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

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

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