Alzheimer%26apos;s disease markers, hypertension, and gray matter damage in normal elderly

作者：Glodzik Lidia^*; Mosconi Lisa; Tsui Wai; de Santi Susan; Zinkowski Raymond; Pirraglia Elizabeth; Rich Kenneth E; McHugh Pauline; Li Yi; Williams Schantel; Ali Fahad; Zetterberg Henrik; Blennow Kaj; Mehta Pankaj; de Leon Mony J

来源：Neurobiology of Aging, 2012, 33(7): 1215-1227.

DOI：10.1016/j.neurobiolaging.2011.02.012

• Aging
• Biomarkers
• MRI
• Alzheimer%26apos
• s disease
• Cerebrospinal fluid
• Hypertension

It is not well known whether Alzheimer%26apos;s disease (AD) cerebrospinal fluid (CSF) biomarkers are associated with brain damage in cognitively normal elderly. The combined influence of CSF biomarkers and hypertension (HTN) on the gray matter (GM) is also not well described. One hundred fifteen cognitively healthy subjects (mean age 62.6 +/- 9.5%, 62% women) received clinical assessment, a high resolution magnetic resonance imaging (MRI), and a lumbar puncture. The CSF levels of total tau (t-tau), hyperphosphorylated tau (p-tau(231)), amyloid beta (A beta 42/A beta 0), p-tau(231)/A beta 42, and t-tau/A beta 42 were dichotomized as %26quot;high%26quot; and %26quot;low%26quot; based on accepted cut off values. Statistical parametric mapping was used to examine MRI scans for regional GM density, studied as a function of the CSF markers, HTN, and combination of both. Global and medial temporal lobe (MTL) GM was also assessed. Voxel based morphometry revealed that higher t-tau was associated with lower GM density in the precunei. Subjects with higher p-tau(231) and p-tau(231)/A beta 42 had less GM in temporal lobes. Low A beta 42/A beta 40 was related to less GM in the thalami, caudate, and midbrain. Subjects with hypertension showed more GM atrophy in the cerebellum, occipital, and frontal regions. Simultaneous presence of elevated CSF AD biomarkers and HTN was associated with more GM atrophy than either marker individually, but no interaction effects were identified. In conclusion, in normal elderly CSF tau markers were associated predominantly with lower GM estimates in structures typically affected early in the AD process. In this presymptomatic stage when no cognitive impairment is present, AD biomarkers and HTN have additive effects on gray matter damage.

• 出版日期2012-7