[Show abstract][Hide abstract] ABSTRACT: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).
Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.
Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.
Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.
Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.
The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.
Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.
JAMA The Journal of the American Medical Association 05/2015; 313(9):1924-1938. DOI:10.1001/jama.2015.4668 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
One of the interesting features of the amyloid tracer Pittsburgh compound B (PiB) is that it generates a signal in the white matter (WM) in both healthy subjects and cognitively impaired individuals. This characteristic gave rise to the possibility that PiB could be used to trace WM pathology. In a group of cognitively healthy elderly we examined PiB retention in normal-appearing WM (NAWM) and WM lesions (WML), one of the most common brain pathologies in aging.
We segmented WML and NAWM on fluid attenuation inversion recovery (FLAIR) images of 73 subjects (age 61.9 ± 10.0, 71 % women). PiB PET images were corrected for partial volume effects and coregistered to FLAIR images and WM masks. WML and NAWM PiB signals were then extracted.
PiB retention in WML was lower than in NAWM (p
European journal of nuclear medicine and molecular imaging 10/2014; 42(1). DOI:10.1007/s00259-014-2897-1 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Postoperative cognitive dysfunction (POCD) may be a complication after surgery in the elderly. The etiology of POCD remains unclear. Tissue damage activates the peripheral immune system resulting in the release of inflammatory mediators. Neuro-inflammation can be accompanied by cognitive dysfunction. Inflammatory markers may be useful in predicting those individuals at a greater risk of developing dementia. We sought to determine whether the degree of preoperative inflammatory burden would have an effect on the progression of POCD at 6 months.
These prospective findings suggest that the subgroup of elderly patients, with a relatively increased baseline inflammatory burden, are most at risk at six months after surgery for a negative impact upon attention and concentration. As measured by the Digit Span Forward test. The identification of a specific subgroup of patients who are predisposed to POCD raises the possibility of optimizing patient inflammatory status preoperatively. Or of modulating the immune system perioperatively.
[Show abstract][Hide abstract] ABSTRACT: In hypertension (HTN), cerebral blood flow regulation limits are changed, and the threshold for blood pressure (BP) at which perfusion is safely maintained is higher. This shift may increase the brain's vulnerability to lower BP in subjects with vascular disease. We investigated whether longitudinal reduction in mean arterial pressure (MAP) was related to changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. The relationships among MAP, memory decline, and hippocampal atrophy were also examined. Seventy-seven subjects (age 63.4 ± 9.4, range 44-86 years; education 16.9 ± 2.1, range 10-22 years; 60% women) were assessed twice, 2 ± 0.5 years apart. At both time points, all subjects underwent full medical and neuropsychological evaluations, lumbar punctures, and magnetic resonance imaging examinations. Twenty-five subjects had HTN. Hyper- and normotensive subjects did not differ in their CSF biomarkers, hippocampal volumes (HipVs), or memory scores at baseline. In the entire study group, the increase in tau phosphorylated at threonine 181 (p-tau181) was associated with a decline in verbal episodic memory (β = -0.30, p = 0.01) and HipV reduction (β = -0.27, p = 0.02). However, longitudinal decrease in MAP was related to memory decline (β = 0.50, p = 0.01) and an increase in p-tau181 (β = -0.50, p = 0.01) only in subjects with HTN. Our findings suggest that the hypertensive group may be sensitive to BP reductions.
Neurobiology of aging 08/2013; 35(1). DOI:10.1016/j.neurobiolaging.2013.06.011 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Numerous studies have shown that Alzheimer's Disease (AD) pathology begins before the onset of clinical symptoms. Because therapies are likely to be more effective if they are implemented early in the disease progression, it is necessary to identify reliable biomarkers to detect AD pathology in the early stages of the disease, ideally in presymptomatic individuals. Recent research has identified three candidate cerebrospinal fluid (CSF) biomarkers that reflect AD pathology: amyloid beta, total tau protein (t-tau), and tau protein phosphorylated at AD-specific epitopes (p-tau). They are useful in supporting the AD diagnosis and have predictive value for AD when patients are in the stage of mild cognitive impairment (MCI). However, their predictive utility in cognitively healthy subjects is still being evaluated. We conducted a review of studies published between 1993 and 2011 and summarized their findings on the role of CSF biomarkers for AD in healthy elderly.
Frontiers in Bioscience 06/2013; 18(3):1150-73. DOI:10.2741/4170 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
One of the complications resulting from surgery in the elderly is post-operative cognitive dysfunction (POCD) (1, 2). We sought to determine if patients with pre-existing mild cognitive impairment (MCI) would have accelerated progression of dementia post-operatively when compared to a non-impaired control group without MCI.
We believe there may be an association between particular cognitive domains and post-operative status.