Abstract. The aim of the study is to evaluate whether depression or apathy in patients with amnestic-mild cognitive impairment (MCI) increases the risk of progressing to Alzheimer's disease (AD). We investigated 131 consecutive memory-clinic outpatients with newly-diagnosed amnestic-MCI (mean age 70.8, SD = 6.5). Psychiatric disorders were diagnosed at baseline according to the criteria for depression and apathy in AD. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI). Follow-up examinations were conducted after six months and annually for four years. Neurologists diagnosed AD at follow-up using NINCDS-ADRDA criteria. Cox proportional hazard models with 95% confidence intervals were used to test the hypothesis that apathy or depression increases the risk of developing AD. At baseline, 36.6% amnestic-MCI patients had a diagnosis of depression and 10.7% had apathy. Patients with both amnestic-MCI and an apathy diagnosis had an almost sevenfold risk of AD progression compared to amnestic-MCI patients without apathy (HR = 6.9; 2.3-20.6), after adjustment for age, gender, education, baseline global cognitive and functional status, and depression. Furthermore, the risk of developing AD increased 30% per point on the NPI apathy item (HR = 1.3; 1.1-1.4). There was no increased risk of developing AD in amnestic-MCI patients with either a diagnosis or symptoms of depression. In conclusion, apathy, but not depression, predicts which patients with amnestic-MCI will progress to AD. Thus, apathy has an important impact on amnestic-MCI and should be considered a mixed cognitive/psychiatric disturbance related to ongoing AD neurodegeneration.

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline with loss of memory. In the last years there has been a great interest on the early phases of AD, trying to identify the pathogenic mechanisms of AD and define early treatment modalities. In particular, Mild Cognitive Impairment (MCI) is attractive because it represents a transitional state between normal aging and dementia, although not all MCI patients automatically convert to AD. The neurotrophin brain-derived neurotrophic factor (BDNF) is critical for survival and function of neurons that degenerate in AD and represents a potential neuroprotective agent. However, opposite data on serum levels of BDNF have been reported in AD patients, probably reflecting differences in patient recruitment and stage of the disease. Thus, in this study we measured BDNF serum levels in AD patients (with different degree of severity), MCI patients and healthy subjects. We found that serum BNDF levels were significantly increased in MCI and AD patients when compared to healthy subjects and this increase in AD patients was neither dependent on illness severity, nor on treatment with Acetylcholinesterase inhibitors and/or antidepressant medications. Our findings indicate that BDNF serum levels increase in MCI and AD patients, supporting the hypothesis of an upregulation of BDNF in both preclinical phase of dementia (MCI) and clinical stages of AD. Other studies are necessary to establish a direct link between BDNF peripheral levels and AD longitudinal course, as well as the role of other factors, such as blood cell activation, in determining these events.

In this study, diffusion tensor imaging (DTI) and T* 2 multiecho relaxometry were combined in 30 healthy subjects at 3T, with the aim of characterizing the spatial distribution of relaxation rates in white matter (WM). Region of interest (ROI) analysis was performed in 23 different fiber tracts automatically defined in standard space. Spearman rank analysis was performed on regional values of T* 2 , fractional anisotropy (FA), and radial diffusivity (RD). A strong relationship was observed between the location and direction of fiber bundles and relaxation rates, and adjacent fiber bundles with similar orientation showed very different relaxation rates. Moreover, while relaxation rates varied largely between different fiber tracts, variation of the same parameter within the same anatomical fiber bundle across individuals was remarkably limited. The rich variability of relaxation rates in WM and their complex relationship with DTI data suggested that the two techniques might be sensitive to complementary characteristics of myelin structure. This has tremendous potential to allow for a more detailed understanding of brain development and pathology, in particular in the context of age-related cognitive decline. Magn Reson Med 61: 1066 -1072, 2009.

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