title: Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease.
abstract: Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.
authors.affiliation: LET'S-ISTC-CNR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy.|University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Fenne Margreeth
authors.initials: FM
authors.lastname: Smits
authors.affiliation: LET'S-ISTC-CNR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy.|Institute of Neuroscience, Newcastle University, Medical School, Newcastle upon Tyne, United Kingdom.|Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porcaro
authors.affiliation: LET'S-ISTC-CNR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cottone
authors.affiliation: LET'S-ISTC-CNR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy.|Institute of Neurology, Cattolica del Sacro Cuore University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cancelli
authors.affiliation: Institute of Neurology, Cattolica del Sacro Cuore University, Rome, Italy.|Unit of Neuroimaging, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: LET'S-ISTC-CNR, Ospedale Fatebenefratelli, Isola Tiberina, Rome, Italy.|Unit of Neuroimaging, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Tecchio
mesh_terms: D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000473:pathology; D004569:Electroencephalography; D005260:Female; D017709:Fractals; D006801:Humans; D008297:Male