Dementia is a major cause of disability among the elderly, with Alzheimer disease being responsible for about 70% of cases. Age, family history, and the presence of the apolipoprotein E ε4 allele have been found to be significant risk factors for the development of Alzheimer disease and all-cause dementia.^1-3 More recently, a high plasma concentration of homocysteine has also been shown to be a risk factor for Alzheimer disease and dementia.⁴

Background: Elevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Methods and Results: Plasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C. Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42; P <0.0001) was in the model. These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non–high‐density lipoprotein cholesterol, in contrast to LDL triglycerides. Conclusions: sdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

Dementia is a progressive neurodegenerative disorder that is clinically characterized by loss of memory and cognitive decline. According to the World Alzheimer Report, currently about 36 million people worldwide are affected by dementia and it is estimated that this number will nearly double over the next 20 years. Of all forms of dementia, Alzheimer disease (AD) is the most common, comprising up to 80% in the elderly population.

Objective: We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls.Methods: Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participants of the Framingham Offspring Study, including 173 men and 74 women with CHD.Results: Postmenopausal status and male sex were associated with higher sdLDL-C concentrations (P < 0.0001). Cholesterol-lowering medication use was more frequent (P < 0.0001) in CHD patients than in controls (46.8% vs 11.4% in men; 35.1% vs 8.8% in women). In men, mean LDL-C was lower in CHD than in controls (3.22 vs 3.51 mmol/L, P < 0.0001), whereas mean sdLDL-C concentrations were similar (0.83 vs 0.84 mmol/L, P = 0.609). In women, mean LDL-C was similar in CHD and controls (3.53 vs 3.46 mmol/L, P = 0.543), but mean sdLDL-C was higher (0.83 vs 0.68 mmol/L, P = 0.0015). The mean percentage of LDL-C as sdLDL-C was higher in both men and women with CHD than controls (P < 0.01). Increased LDL-C and sdLDL-C were found in 10.4% and 22.0% of men and in 24.3% and 27.8% of women with CHD, respectively.Conclusions: Despite 4-fold greater cholesterol-lowering therapy use, CHD patients had mean LDL-C concentrations above the LDL-C goal of <2.6 mmol/L (<100 mg/dL). Although women with CHD had higher sdLDL-C concentrations than controls, this difference was not seen in men. These findings may explain some of the high residual risk of future CHD events in CHD patients.

Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in differe

Cerebrotendinous xanthomatosis (CTX) is a rare disorder due to defective sterol 27-hydroxylase causing a lack of chenodeoxycholic acid (CDCA) production and high plasma cholestanol levels. Our objective was to review the diagnosis and treatment results in 43 CTX cases. We conducted a careful review of the diagnosis, laboratory values, treatment, and clinical course in 43 CTX cases. The mean age at diagnosis was 32 years; the average follow-up was 8 years. Cases had the following conditions: 53% chronic diarrhea, 74% cognitive impairment, 70% premature cataracts, 77% tendon xanthomas, 81% neurologic disease, and 7% premature cardiovascular disease. The mean serum cholesterol concentration was 190 mg/dL; the mean plasma cholestanol level was 32 mg/L (normal <5.0 mg/L), which decreased to 6.0 mg/L (-81%) with CDCA therapy generally given as 250 mg orally 3 times daily. Of those tested on treatment, 63% achieved cholestanol levels of <5.0 mg/L; 91% had normal liver enzyme levels; none had significant liver problems after dose adjustment. Treatment improved symptoms in 57% at follow-up, but 20% with advanced disease continued to deteriorate. In the United States, CDCA has been approved for gallstone dissolution, but not for CTX despite long-term efficacy and safety data. Health care providers seeing young patients with tendon xanthomas and relatively normal cholesterol levels, especially those with cataracts and learning problems, should consider the diagnosis of CTX so they can receive treatment. CDCA should receive regulatory approval to facilitate therapy for the prevention of the complications of the disease.