Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer’s disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and Alzheimer’s Disease”. The scientific sessions of the workshop focused on age-related and neuropathological changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the CNS are affected by Alzheimer pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses.

Background: White matter hyperintensity (WMH) change on brain MRI is observed with increased

MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.

Objective: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders.Methods: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n ϭ 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes.Results: Mean age was 87 Ϯ 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine -3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine -3 pattern and white matter hyperintensity volume. Conclusion:Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population. Neurology The epidemiology of Alzheimer disease (AD) suggests a role for nutrition. [1][2][3][4][5][6][7] Despite studies in favor of a single or a few nutrients in the prevention of AD, the translation to formal clinical trials testing vitamin E, B vitamins, or docosahexaenoic acid have been disappointing. [8][9][10][11][12] Given the interactive nature of nutrient action and metabolism, it is not surprising that a single or few nutrient approaches for neurodegenerative disease are tenuous. [13][14][15] These results impart the rationale for novel methodologic approaches that appreciate the interactive features of nutrients and model their collective influence in the promotion of brain health.Food frequency questionnaires (FFQ) have traditionally been used to construct dietary patterns.16 FFQ is relatively inexpensive and fairly comprehensive, but this method is subject to faulty recall of dietary intake and does not account for variability in nutrient absorption, both of which are issues in the elderly. 17,18 We have recently reported a reliable blood test that assesses nutritional status in people at risk for dementia. 19 In the current study, we examine the relationship of nutrient biomarkers with cognitive function and MRI.To capture the effect of nutrients in combination, we construct nutrient biomarker patterns using principal component analysis (PCA). Cluster analysis, 20 index scores, 21 and reduced rankFrom the

Objective: To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation.Methods: Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and .1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p , 0.1.Results: Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p 5 0.003).Conclusion: Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter. Disruption of white matter integrity, frequently observed as white matter hyperintensities (WMH) on T2-weighted MRI sequences, has detrimental effects on cognitive function, motor performance, and functional status in the elderly [1][2][3] and is associated with increased risk of all types of dementia, including Alzheimer disease (AD).4 Furthermore, WMH accumulation over time has been shown to increase risk of cognitive decline. 3,[5][6][7] While the general consensus is that the etiology of white matter accumulation is secondary to small-vessel ischemic changes, [8][9][10][11][12][13] it is not well established whether those with faster WMH accumulation may have contributions from other pathologies. Because accumulation of WMH increases risk of cognitive decline, identifying the pathologic correlates of faster WMH accumulation could potentially guide interventions targeting specific risks for prevention and treatment to preserve cognitive function in the elderly. Furthermore, while there are previous observations supporting a link between cerebrovascular disease (CVD) and AD, 14 it is not clearly established whether WMH progression is associated with neurodegenerative changes of AD. Thus, our aim was to bette...