Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial.

Aims: Low-density lipoprotein cholesterol (LDL-C) predicts heart disease onset and may be reduced by intermittent fasting. Some studies, though, reported that fasting increased LDL-C; however, no study evaluated LDL-C as the primary endpoint. This randomized controlled trial evaluated the effect of low-frequency intermittent fasting on LDL-C and other biomarkers. Methods and results: Adults aged 21-70 years were enrolled who were not taking a statin, had modestly elevated LDL-C, had ≥1 metabolic syndrome feature or type 2 diabetes, and were not taking anti-diabetic medication (N = 103). Water-only 24-h fasting was performed twice weekly for 4 weeks and then once weekly for 22 weeks; controls ate ad libitum. The primary outcome was 26-week LDL-C change score. Secondary outcomes (requiring P ≤ 0.01) were 26-week changes in homeostatic model assessment of insulin resistance (HOMA-IR), Metabolic Syndrome Score (MSS), brain-derived neurotrophic factor (BDNF), and MicroCog general cognitive proficiency index (GCPi). Intermittent fasting (n = 50) and control (n = 53) subjects were, respectively, aged 49.3 ± 12.0 and 47.0 ± 9.8 years, predominantly female (66.0% and 67.9%), and overweight (103 ± 24 and 100 ± 21 kg) and had modest LDL-C elevation (124 ± 19 and 128 ± 20 mg/dL). Drop-outs (n = 12 fasting, n = 20 control) provided an evaluable sample of n = 71 (n = 38 fasting, n = 33 control). Intermittent fasting did not change LDL-C (0.2 ± 16.7 mg/dL) vs. control (2.5 ± 19.4 mg/dL; P = 0.59), but it improved HOMA-IR (-0.75 ± 0.79 vs. -0.10 ± 1.06; P = 0.004) and MSS (-0.34 ± 4.72 vs. 0.31 ± 1.98, P = 0.006). BDNF (P = 0.58), GCPi (P = 0.17), and weight (-1.7 ± 4.7 kg vs. 0.2 ± 3.5 kg, P = 0.06) were unchanged. Conclusions: A low-frequency intermittent fasting regimen did not reduce LDL-C or improve cognitive function but significantly reduced both HOMA-IR and MSS. Trial registration: clinicaltrials.gov, NCT02770313.

Cognitive Screening Tools for Late Career Physicians: A Critical Review.

Screening measures are widely used in medicine to assess the increased probability that members of a defined population have a particular condition and therefore require more extensive assessment. The rationale for prospective screening of late career physicians (LCPs) is drawn from the following circumstances: Senior physicians-prone to the vicissitudes of aging-comprise nearly a third of the US physician workforce, physicians are poor at self-evaluation, data suggest many have clinically relevant cognitive decline, and screening is an evidence-based, method to detect individuals at risk and determine whether a comprehensive evaluation is necessary. A handful of professional organizations (eg, surgeons, obstetricians, and a growing number of medical staff credentialing committees) have developed policies in this arena. This focused review compares cognitive screening methods used or recommended for LCPs, with particular attention to the psychometric properties, ease of operational implementation, and appropriate application to physicians-a population selected for high cognitive reserve and skills. Further, we identify gaps in knowledge and practice, including the need for more career-span normative data on physicians' cognitive and work performance. Stakeholders can improve rehabilitation and other supports to LCPs in transition, calling upon the unique expertise of those neuropsychologists who are trained on conducting fitness for duty evaluations, as well as rehabilitation professionals who can assist in developing modifications to practice when indicated or facilitate graceful transitions to retirement when necessary.

Visual and Verbal Serial List Learning in Patients with Statistically-Determined Mild Cognitive Impairment.

BACKGROUND AND OBJECTIVE: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes. RESEARCH DESIGN AND METHODS: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively. RESULTS: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored better than other groups on all parameters. aMCI and mixed/dys MCI did not differ on immediate or delayed free recall. Both delayed BVMT-R and P(r)VLT recognition test performance dissociated all three groups. Logistic regression analyses found that BVMT-R delayed free recall and delayed recognition scores correctly classified more patients with MCI (75.40%) than analogous P(r)VLT scores (66.20%). Visual versus verbal memory within-group analyses found no differences among non-MCI patients; P(r)VLT immediate free recall was worse among aMCI patients, but BVMT-R immediate free recall and delayed recognition were worse among mixed/dys MCI patients. DISCUSSION AND IMPLICATIONS: Between-group analyses found convergent patterns of performance such that both tests identified elements of amnesia. However, logistic and within-group analyses found differing performance patterns suggesting that impaired visual episodic memory performance may be specific to emergent illness in mixed/dys MCI. Complementary but divergent neurocognitive networks may underlie visual versus verbal episodic memory performance in some patients with MCI.

Development, validity, and normative data study for the 12-word Philadelphia Verbal Learning Test [czP(r)VLT-12] among older and very old Czech adults.

The aim of the present study was to assess the validity of a 12-word Czech version of the Philadelphia (repeatable) Verbal Learning Test [czP(r)VLT-12]. The construction of the czP(r)VLT-12 was modeled after the California Verbal Learning Test (CVLT) and the nine-word Philadelphia (repeatable) Verbal Learning Test [P(r)VLT]. The czP(r)VLT-12 was constructed from a large corpus of old (60-74) and very old (75-96) Czech adults (n = 540). Participants met strict inclusion criteria for the absence of any active or past neurodegenerative disorders and performed within normal limits on other neuropsychological measures. Principal component analysis (PCA) and correlations between czP(r)VLT-12 factor structure and other memory tests were conducted. The czP(r)VLT-12 produced a four-factor solution, accounting for 70.90% of variance, with factors related to: (1) recall, (2) extra-list intrusion errors/recognition foils, (3) interference, and (4) acquisition rate; a solution similar to the CVLT and P(r)VLT. Increasing age resulted in a decline in most czP(r)VLT-12 indices, women outperformed men, and higher education led to higher scores. Memory performance in normal aging did not correlate with instrumental activities of daily living. Low, but significant, correlations were seen with other tests of cognitive performance (divergent validity). Appendices are available that provide normed percentile estimates of individual czP(r)VLT-12 performance stratified by age, education, and gender. In accordance with previous studies, these results demonstrate the usefulness of czP(r)VLT-12 in assessing declarative memory in older adults.

Leukoaraiosis severity and list-learning in dementia.

In patients with dementia, leukoaraiosis (LA) was hypothesized to result in differential patterns of impairment on a verbal serial list-learning test. Using a visual rating scale, 144 dementia patients with ischemic scores <4 were re-categorized as having mild (n = 73), moderate (n = 44), or severe LA (n = 27). Mild LA was predicted to be associated with an amnestic list-learning profile, while severe LA was predicted to be associated with a dysexecutive profile. List-learning performances were standardized to a group of healthy older adults (n = 24). Analyses were conducted on a set of four factors derived from the list-learning paradigm, as well as error scores. Data indicate that LA severity is an important marker for understanding list learning in dementia.

The neuropsychological profile of vascular cognitive impairment--no dementia: comparisons to patients at risk for cerebrovascular disease and vascular dementia.

Hachinski and co-workers have used the term vascular cognitive impairment-no dementia (VaCIND) to represent the earliest stages of cognitive decline associated with vascular changes [Neurology 57 (4) (2001) 714]. However, the neuropsychological profile of vascular CIND remains unclear. Twenty-five healthy elders, 29 individuals at risk for cerebrovascular disease (R-CVD), 18 individuals with VaCIND, and 26 individuals with vascular dementia (VaD) were examined to determine whether patterns of neuropsychological assessment performance can assist in the differentiation of patients at varying levels of risk and severity for cerebrovascular disease and VaD. The R-CVD group performed within normal expectations on most cognitive measures as compared to the elderly control sample and published clinical norms. Relative to elderly controls, the VaCIND group demonstrated significant difficulties on measures of cognitive flexibility, verbal retrieval, and verbal recognition memory, but not on measures of confrontational naming or verbal fluency. The VaD group was impaired on all cognitive measures assessed. The current findings suggest that poor cognitive flexibility and verbal retrieval in the context of preserved function in other domains may characterize the prodromal stage of VaD.

Defining the diagnosis of vascular dementia.

Vascular dementia (VaD) is a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathologic changes. As such, the VaD literature lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes. We address the issues articulated by Paul and colleagues (Paul, Garrett, & Cohen, 2003), by offering four recommendations to refine the clinical assessment and diagnostic decision-making process of individuals with suspected cerebrovascular changes: (a) Describing the nature of vascular changes may facilitate predictions regarding the neuropsychological profile of subtypes of VaD; (b) employ a process approach to assessment, measuring cognitive constructs in addition to test scores to describe the neuropsychological profiles of types of VaD; (c) integrate direct MRI observations of the brain and other collateral data in the diagnostic process; and (d) consider using "vascular cognitive impairment, no dementia" for suspected prodromal VaD.