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White matter hyperintensities (WMH) is mainly caused by cerebrovascular injury and may also increase the possibilities of progression to Alzheimer's disease. The present study aims to determine whether plasma neurofilament light (NFL) protein levels could predict the progression of WMH volume in elderly persons without dementia. The present study enrolled 1029 non-dementia participants from the Alzheimer's Disease Neuroimaging Initiative in which all had measurements of plasma NFL and WMH at baseline and 589 had longitudinal measurements during follow-up. Spearman correlation analyses and regression models were used to assess cross-sectional and longitudinal associations between plasma NFL and WMH. Plasma NFL concentration had a moderately strong correlation with WMH at baseline (r = 0.17, p < 0.001). Longitudinal analyses showed that higher baseline plasma NFL concentration was associated with accelerated progression of WMH (β=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the future (β=0.581, p = 0.002). The results of the study suggest that plasma NFL level might be used as a noninvasive biomarker to track variation trend in WMH in elderly persons without dementia.

Background The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism emerged as a risk factor for Alzheimer's disease (AD). However, little was known about its effects on the process of potential AD. Objective To explore the effects of the Val66Met polymorphism on cognition, cerebrospinal fluid (CSF), and neuroimaging markers in non-demented elderly individuals. Methods A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test the influence of BDNF Val66Met polymorphism on cognitive impairment, brain structure atrophy, and change in the levels of CSF biomarkers. Moreover, we also conducted our study in abnormal amyloid-β (A+) subgroup and normal amyloid-β (A-) subgroup, as well as in APOEɛ4 carriers and non-carriers. Results The BDNF Val66Met polymorphism had significant association with atrophy of the entorhinal cortex and Mini-Mental State Examination (MMSE) scores in the non-demented elderly and A + subgroup, while no association was found in A-subgroup. What is more, there was a significant effect of interaction between BDNF Val66Met and amyloid-β load in MMSE. In addition, significant associations of BDNF Val66Met with the entorhinal cortex and ventricular volumes were found among APOEɛ4 non-carriers, but not APOEɛ4 carriers. Conclusions The BDNF Val66Met polymorphism is associated with cognitive impairment and brain atrophy among the non-demented elderly, APOEɛ4 non-carriers and A + subgroup, implying the potential of the Val66Met polymorphism as an important genetic factor for AD-related neurodegeneration.

BACKGROUND Vascular dementia (VaD) is the second most common type of dementia. So far, little is known about the contribution of genetic polymorphisms to the risk of VaD. Many candidate genetic polymorphisms have been examined in a large number of studies. However, due to the conflicting results, the genetics of VaD is still behind the shadow. OBJECTIVE We conducted a comprehensive meta-analysis on associations between genetic polymorphisms of any gene and VaD to investigate the genetics of VaD. METHOD We sought the published studies of associations between any genetic polymorphism and VaD and critically appraised them. We assessed the effects of genetic models by calculating pooled odds ratios (ORs), investigating the origin of heterogeneity by subgroup analysis, and testing the robustness by random effect model and sensitivity analysis. RESULTS 69 studies with 4,462 cases and 11,583 controls were included. We identified APOE ɛ2/ɛ3/ɛ4 and additional four genetic polymorphisms including MTHFR C677T, PON1 L55M, TGF-β1 +29C/T, and TNF-α -850C/T associated with VaD. Tested by random effect model and sensitivity analysis, the pooled results show nice robustness. CONCLUSIONS Our comprehensive meta-analysis highlighted the genetic contribution to sporadic VaD. Because of the small amount of data on associations between genetic polymorphisms, except for APOE, and VaD, more studies are needed to test the existing genetic polymorphisms and detect other related genetic variants.