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Mind & Brain, the Journal of Psychiatry

life NPS without MCI. The cognitive and clinical profiles of MCI with and without NPS converting or not to dementia shall be investigated in large samples, using longitudinal study designs and standardized cognitive and mood measu- res. The recent development of biomarkers for the in vivo assessment of amyloid-beta and tau, the proteins defining AD,55 together with thorough cognitive and NPS evaluations, will eventually contribute to a better understanding of the pathophysiological substrate underlying the relationship between NPS, MCI, and dementia.

Regarding the possible mechanisms underlying the link between affective symptoms and dementia, several hypoth- eses involving vascular changes in the frontostriatal circuits,46 modifications of the hypothalamicpituitaryadrenal axis (hypercortisolemia) affecting the limbic system and frontal cortex,56 as well as decreased levels of serotonin,57 were formulated to account for depression, chronic stress, and cognitive decline in MCI and AD patients. In addition, a recent cerebral FDDNP-PET study58 demonstrated a relation- ship between severity of depressive and anxiety symptoms and FDDNP binding values in the temporal lobe and posterior cingulate of MCI and healthy middle-aged and older adults. FDDNP is a molecule that binds to amyloid plaques (AP) and neurofibrillary tangles (NFT). These results suggest a rela- tionship between relatively mild mood symptoms and biomarkers of cerebral AP and NFT that may vary according to the degree of cognitive impairment. Taken together, these results suggest that in patients with affective symptoms with and without MCI, AP and NFT may be present in brain areas related to psychological distress.

In 2006, The National Institute of Mental Health Panel Experts59 appropriately underlined that the most consistent findings in this regard were structural measures (eg, regional atrophy and mediotemporal atrophy), positron emission tomography functional measures, and several promising cerebrospinal fluid measures. ApoE genotype is the most consistent genetic marker, but others are being examined. According to these experts, future research will need to reconcile the divergent paths of research regarding the underlying pathologic features seen on neuroimaging.

Acknowledgements: Acknowledgments: The author thanks Alex-

andre St-Hilaire for his precious assistance in the preparation of this manuscript.

Disclosure: I declare thatl have no competing interests. The

research work of Dr Simard is currendy funded by a regular research grant from the Alzheimer Society of Canada (#09 37) and she is also engaged in research funded by the Canadian Institutes of Health Research-Institute of Aging.


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