Subtypes of Alzheimer's Disease Display Distinct Network Abnormalities Extending Beyond Their Pattern of Brain Atrophy

Different subtypes of Alzheimer's disease (AD) with characteristic distributions of neurofibrillary tangles and corresponding brain atrophy patterns have been identified using structural magnetic resonance imaging (MRI). However, the underlying biological mechanisms that determine this differential expression of neurofibrillary tangles are still unknown. Here, we applied graph theoretical analysis to structural MRI data to test the hypothesis that differential network disruption is at the basis of the emergence of these AD subtypes. We studied a total of 175 AD patients and 81 controls. Subtyping was done using the Scheltens' scale for medial temporal lobe atrophy, the Koedam's scale for posterior atrophy, and the Pasquier's global cortical atrophy scale for frontal atrophy. A total of 89 AD patients showed a brain atrophy pattern consistent with typical AD; 30 patients showed a limbic-predominant pattern; 29 patients showed a hippocampal-sparing pattern; and 27 showed minimal atrophy. We built brain structural networks from 68 cortical regions and 14 subcortical gray matter structures for each AD subtype and for the controls, and we compared between-group measures of integration, segregation, and modular organization. At the global level, modularity was increased and differential modular reorganization was detected in the four subtypes. We also found a decrease of transitivity in the typical and hippocampal-sparing subtypes, as well as an increase of average local efficiency in the minimal atrophy and hippocampal-sparing subtypes. We conclude that the AD subtypes have a distinct signature of network disruption associated with their atrophy patterns and further extending to other brain regions, presumably reflecting the differential spread of neurofibrillary tangles. We discuss the hypothetical emergence of these subtypes and possible clinical implications

Low carbohydrate diets in family practice: what can we learn from an internet-based support group

The Active Low-Carber Forums (ALCF) is an on-line support group started in 2000 which currently has more than 86,000 members. Data collected from posts to the forum and from an on-line survey were used to determine the behavior and attitudes of people on low carbohydrate diets. Members were asked to complete a voluntary 27-item questionnaire over the internet. Our major findings are as follows: survey respondents, like the membership at large, were mostly women and mostly significantly overweight, a significant number intending to and, in many cases, succeeding at losing more than 100 lbs. The great majority of members of ALCF identify themselves as following the Atkins diet or some variation of it. Although individual posts on the forum and in the narrative part of our survey are critical of professional help, we found that more than half of respondents saw a physician before or during dieting and, of those who did, about half received support from the physician. Another 28 % found the physician initially neutral but supportive after positive results were produced. Using the same criteria as the National Weight Registry (without follow-up) – 30 lbs or more lost and maintained for more than one year – it was found that more than 1400 people had successfully used low carb methods. In terms of food consumed, the perception of more than half of respondents were that they ate less than before the diet and whereas high protein, high fat sources replaced carbohydrate to some extent, the major change indicated by survey-takers is a large increase in green vegetables and a large decrease in fruit intake. Government or health agencies were not sources of information for dieters in this group and a collection of narrative comments indicates a high level of satisfaction, indeed enthusiasm for low carbohydrate dieting. The results provide both a tabulation of the perceived behavior of a significant number of dieters using low carbohydrate strategies as well as a collection of narratives that provide a human perspective on what it is like to be on such a diet. An important conclusion for the family physician is that it becomes possible to identify a diet that is used by many people where the primary principle is replacement of starch and sugar-containing foods with non-starchy vegetables, with little addition of fat or protein. Used by many people who identify themselves as being on the Atkins diet, such a strategy provides the advantages of carbohydrate-restricted diets but is less iconoclastic than the popular perception and therefore more acceptable to traditional nutritionists. It is reasonable for family practitioners to turn this observation into a recommendation for patients for weight control and other health problems

(Dis-)Connected Dots in Dementia with Lewy Bodies—A Systematic Review of Connectivity Studies

Studies on dementia with Lewy bodies (DLB) have mainly focused on the degeneration of distinct cortical and subcortical regions related to the deposition of Lewy bodies. In view of the proposed trans-synaptic spread of the α-synuclein pathology, investigating the disease only in this segregated fashion would be detrimental to our understanding of its progression. In this systematic review, we summarize findings on structural and functional brain connectivity in DLB, as connectivity measures may offer better insights on how the brain is affected by the spread of the pathology. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched Web of Science, PubMed, and SCOPUS for relevant articles published up to November 1, 2021. Of 1215 identified records, we selected and systematically reviewed 53 articles that compared connectivity features between patients with DLB and healthy controls. Structural and functional magnetic resonance imaging, positron emission tomography, single-positron emission computer tomography, and electroencephalography assessments of patients revealed widespread abnormalities within and across brain networks in DLB. Frontoparietal, default mode, and visual networks and their connections to other brain regions featured the most consistent disruptions, which were also associated with core clinical features and cognitive impairments. Furthermore, graph theoretical measures revealed disease-related decreases in local and global network efficiency. This systematic review shows that structural and functional connectivity characteristics in DLB may be particularly valuable at early stages, before overt brain atrophy can be observed. This knowledge may help improve the diagnosis and prognosis in DLB as well as pinpoint targets for future disease-modifying treatments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age and is associated with obesity, hyperinsulinemia, and insulin resistance. Because low carbohydrate diets have been shown to reduce insulin resistance, this pilot study investigated the six-month metabolic and endocrine effects of a low-carbohydrate, ketogenic diet (LCKD) on overweight and obese women with PCOS. RESULTS: Eleven women with a body mass index >27 kg/m(2 )and a clinical diagnosis of PCOS were recruited from the community. They were instructed to limit their carbohydrate intake to 20 grams or less per day for 24 weeks. Participants returned every two weeks to an outpatient research clinic for measurements and reinforcement of dietary instruction. In the 5 women who completed the study, there were significant reductions from baseline to 24 weeks in body weight (-12%), percent free testosterone (-22%), LH/FSH ratio (-36%), and fasting insulin (-54%). There were non-significant decreases in insulin, glucose, testosterone, HgbA1c, triglyceride, and perceived body hair. Two women became pregnant despite previous infertility problems. CONCLUSION: In this pilot study, a LCKD led to significant improvement in weight, percent free testosterone, LH/FSH ratio, and fasting insulin in women with obesity and PCOS over a 24 week period

In vivo 1H-magnetic resonance spectroscopy can detect metabolic changes in APP/PS1 mice after donepezil treatment

<p>Abstract</p> <p>Background</p> <p>Donepezil improves cognitive functions in AD patients. Effects on the brain metabolites N-acetyl-L-aspartate, choline and <it>myo-</it>inositol levels have been reported in clinical studies using this drug. The APP/PS1 mouse coexpresses the mutated forms of human β-amyloid precursor protein (APP) and mutated human presenilin 1 (PS1). Consequently, the APP/PS1 mouse model reflects important features of the neurochemical profile in humans. <it>In vivo </it>magnetic resonance spectroscopy (¹H-MRS) was performed in fronto-parietal cortex and hippocampus (ctx/hipp) and in striatum (str). Metabolites were quantified using the LCModel and the final analysis was done using multivariate data analysis. The aim of this study was to investigate if multivariate data analysis could detect changes in the pattern of the metabolic profile after donepezil treatment.</p> <p>Results</p> <p>Significant differences were observed in the metabolic pattern of APP/PS1 mice in both str and ctx/hipp before and after donepezil treatment using multivariate data analysis, evidencing a significant treatment effect. A treatment effect was also seen in wild type (wt) mice in str. A significant decrease in the metabolic ratio taurine/creatine (Tau/tCr) was related to donepezil treatment (p < 0.05) in APP/PS1 mice in both brain regions. Furthermore, a significant influence on the choline/creatine (tCho/tCr) level was observed in treated APP/PS1 mice compared to untreated in str (p = 0.011). Finally, there was an increase in glutamate/creatine (Glu/tCr) in str in wt mice treated with donepezil.</p> <p>Conclusion</p> <p>Multivariate data analysis can detect changes in the metabolic profile in APP/PS1 mice after donepezil treatment. Effects on several metabolites that are measurable <it>in vivo </it>using MR spectroscopy were observed. Changes in Tau/tCr and tCho/tCr could possibly be related to changed cholinergic activity caused by donepezil treatment.</p

A low-carbohydrate, ketogenic diet to treat type 2 diabetes

BACKGROUND: The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes. METHODS: From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A(1c). RESULTS: Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m(2). Hemoglobin A(1c )decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A(1c). Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly. CONCLUSION: The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication

Kv1.1 null mice have enlarged hippocampus and ventral cortex

BACKGROUND: Mutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy. Mice that express a malfunctional, truncated Kv1.1 (BALB/cByJ-Kv1.1(mceph/mceph)) show a markedly enlarged hippocampus and ventral cortex in adulthood. RESULTS: To determine if mice lacking Kv1.1 also develop a brain enlargement similar to mceph/mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was then studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1(mceph/mceph), BALB/cByJ-Kv1.1(mceph/+), BALB.C3HeB -Kv1.1(-/+ )and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex. CONCLUSION: Total absence of Kv1.1 can induce excessive overgrowth of hippocampus and ventral cortex in mice with a BALB/cByJ background, while mice with one wild type Kv1.1 allele develop normal-sized brains