A periodic fasting diet improves markers of metabolic dysfunction, particularly in people already at risk.

Background: Few longitudinal studies evaluate differences in patterns of change of category compared to letter fluency across the spectrum of cognitive impairment. Methods: We compared change in category (animal and supermarket) and letter (F, A, S) fluency among 239 participants in 3 groups: remained cognitively normal throughout follow-up (n = 96), developed Alzheimer’s Disease (AD; preclinical AD, n = 21), and with AD at initial testing (prevalent AD, n = 122). Results: At baseline, prevalent and preclinical AD groups scored lower on animal than letter fluency. On all fluency measures, the prevalent AD declined faster than other groups (all P < .0001), and preclinical AD declined faster than unimpaired (all P ≤ .02). Overall, animal fluency declined faster than letter fluency; animal fluency declined significantly faster than letter fluency among cognitively normal and prevalent AD participants. Conclusion: Greater longitudinal declines in category compared to letter fluency are consistent with cross-sectional studies. Steeper declines on both fluency measures distinguish preclinical AD from cognitively unimpaired individuals.

Cholesterol, vital to neuronal structure and function, has important roles in the synthesis, deposition, and clearance of β-amyloid (Aβ)^1-3 and may have a pathogenic role in Alzheimer disease (AD). Interest in the potential role of cholesterol is heightened by a series of epidemiologic reports^4-6 that generally demonstrate a correspondence between the atherogenic risk factors for cardiovascular disease and clinically diagnosed AD. In addition, observational studies⁷ have found that statin use is associated with reduced odds of AD. There are also important connections among apolipoprotein E (APOE), Aβ,⁸ and cholesterol. A strong genetic risk factor for AD, the APOE ε4 allele is associated with earlier and higher deposition of Aβ. APOE is the primary transporter of cholesterol in the brain, and its isoforms differentially modulate brain cholesterol levels.⁸ Thus, the potential role of peripheral cholesterol in cerebral Aβ deposition is of interest.

Background: Los Angeles County is a hub for COVID-19 cases in the United States. Academic health centers rapidly deployed and leveraged telemedicine to permit uninterrupted care of patients. Telemedicine enjoys high patient satisfaction, yet little is known about the level of satisfaction during a crisis and to what extent patient- or visit-related factors and trust play when in-person visits are eliminated. Objective: The aim of this study is to examine correlates of patients’ satisfaction with a telemedicine visit. Methods: In this retrospective observational study conducted in our single-institution, urban, academic medical center in Los Angeles, internal medicine patients aged ≥18 years who completed a telemedicine visit between March 10th and April 17th, 2020, were invited for a survey (n=1624). Measures included patient demographics, degree of interpersonal trust in patient-physician relationships (using the Trust in Physician Scale), and visit-related concerns. Statistical analysis used descriptive statistics, Spearman rank-order correlation, and linear and ordinal logistic regression. Results: Of 1624 telemedicine visits conducted during this period, 368 (22.7%) patients participated in the survey. Across the study, respondents were very satisfied (173/365, 47.4%) or satisfied (n=129, 35.3%) with their telemedicine visit. Higher physician trust was associated with higher patient satisfaction (Spearman correlation r=0.51, P<.001). Visit-related factors with statistically significant correlation with Trust in Physician score were technical issues with the telemedicine visit (r=–0.16), concerns about privacy (r=–0.19), concerns about cost (r=–0.23), satisfaction with telemedicine convenience (r=0.41), and amount of time spent (r=0.47; all P<.01). Visit-related factors associated with patients’ satisfaction included fewer technical issues (P<.001), less concern about privacy (P<.001) or cost (P=.02), and successful face-to-face video (P<.001). The only patient variable with a significant positive association was income and level of trust in physician (r=0.18, P<.001). Younger age was associated with higher satisfaction with the telemedicine visit (P=.005). Conclusions: There have been calls for redesigning primary care after the COVID-19 pandemic and for the widespread adoption of telemedicine. Patients’ satisfaction with telemedicine during the COVID-19 pandemic is high. Their satisfaction is shaped by the degree of trust in physician and visit-related factors more so than patient factors. This has widespread implications for outpatient practices and further research into visit-related factors and the patient-provider connection over telemedicine is needed.

Recent epidemiologic studies have noted that risk factors for atherosclerosis (for example, diabetes mellitus, hypertension, and hyperlipidemia) are associated with increased risk of incident Alzheimer's disease (AD). In this evidence-based review, we frame the proposition as a question: are vascular risk factors also risk factors for plaques and tangles or just for concomitant vascular pathology that increases the likelihood of dementia? To date, no representative, prospective studies with autopsy (evidence level A) show significant positive associations between diabetes mellitus, hypertension, or intracranial atherosclerosis and plaques or tangles. Some prospective, representative, epidemiologic studies (evidence level B) show associations between diabetes, hypertension, hyperlipidemia, and aggregated risk factors with clinically diagnosed incident AD. However, the strength of association diminishes in the following order: vascular dementia (VaD) > AD + VaD > AD. This pattern is arguably more consistent with the hypothesis that atherosclerosis promotes subclinical vascular brain injury, thereby increasing the likelihood of dementia and in some cases making symptoms present earlier. Several autopsy studies from AD brain banks (evidence level C) have observed positive associations between intracranial atherosclerosis and severity of plaques and tangles. However, these studies may reflect selection bias; these associations are not confirmed when cases are drawn from non-dementia settings. We conclude that, at the present time, there is no consistent body of evidence to show that vascular risk factors increase AD pathology.

In humans, apolipoprotein E (apoE) has 3 isoforms: apoE2, apoE3, and apoE4. APOE4 is a major genetic risk factor for Alzheimer disease (AD).¹ Apolipoprotein E4 has direct effects on the cerebrovascular system, resulting in microvascular lesions and blood-brain barrier (BBB) damage, as recently reviewed.² Neurovascular dysfunction is also present in cognitively normal APOE4 carriers and individuals with APOE4-associated disorders including AD.^1-3 Moreover, postmortem brain tissue analysis has indicated that BBB breakdown in patients with AD is more pronounced in APOE4 carriers compared with APOE3 or APOE2.^4-6 Our recent studies in transgenic mice have demonstrated that apoE4 leads to BBB breakdown by activating the proinflammatory cyclophilin A (CypA)–matrix metalloproteinase 9 (MMP-9) pathway in brain pericytes, which in turn results in degradation of the BBB tight junctions and basement membrane proteins.⁷ It has also been shown that apoE4-mediated BBB breakdown leads to secondary neuronal injury and cognitive decline in transgenic mice.⁷ Apolipoprotein E2 and apoE3 maintained normal BBB integrity in transgenic mice by suppressing the CypA–MMP-9 pathway.⁷ Here, we studied the cerebrospinal fluid (CSF)/plasma albumin quotient (Q_Alb), an established marker of BBB breakdown,⁸ and CypA and active MMP-9 levels in the CSF of cognitively normal individuals with different APOE genotypes to determine whether apoE4-dependent changes in BBB permeability and CypA–MMP-9 pathway as shown in APOE4, but not APOE3 and APOE2 transgenic mice, also occur in humans.