Cortical thickness, brain metabolic activity, and in vivo amyloid deposition in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease

DUARTE-ABRITTA, BÁRBARA; VILLARREAL, MIRTA F.; ABULAFIA, CAROLINA; LOEWENSTEIN, DAVID; CURIEL CID, ROSIE E.; CASTRO, MARIANA N.; SURACE, EZEQUIEL; SÁNCHEZ, STELLA-MARIS; VIGO, DANIEL E.; VÁZQUEZ, SILVIA; NEMEROFF, CHARLES B.; SEVLEVER, GUSTAVO; GUINJOAN, SALVADOR M.

JOURNAL OF PSYCHIATRIC RESEARCH

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2018 vol. 107 p. 11 - 18

0022-3956

The natural history of preclinical late-onset Alzheimer´s disease (LOAD) remains obscure and has received lessattention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With thepurpose of detecting early structural and functional traits associated with the disorder, we sought to characterizecortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in personsat risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images forgray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detectfibrillar amyloiddeposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed withLOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS).We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of theprefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral me-tabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippo-campal volume and hippocampal metabolism. Given the importance of age in this sample of individuals po-tentially developing early AD-related changes, we controlled results for age and observed that most differencesin cortical thickness and metabolism became nonsignificant; however, greater deposition ofβ-amyloid wasobserved in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior andmiddle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, andamyloid changes in cognitively normal persons with family history of LOAD may bear important implications forthe definition of very early phenotypes of this disorder.1. IntroductionThe pathophysiology of late-onset Alzheimer´s Disease (LOAD), ac-counting for over 99% of cases of AD, is poorly understood and is anactive area of investigation. Available data suggests AD probably resultsfrom a more complex mechanism than the early-onset form describedby Alzheimer (1907)and named after him byKraepelin (1909), eventhough these two clinical forms share the neuropathological landmarkshttps://doi.org/10.1016/j.jpsychires.2018.10.008Received 28 March 2018; Received in revised form 30 August 2018; Accepted 4 October 2018∗Corresponding author. Service of Psychiatry, Fleni Foundation Montañeses 2325 5thfloor, C1428AQK, Buenos Aires, Argentina.1Both authors contributed equally to this paper.E-mail address:sguinjoan@fleni.org.ar(S.M. Guinjoan).Journal of Psychiatric Research 107 (2018) 11?180022-3956/ © 2018 Elsevier Ltd. All rights reserved.T