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.
Highlights
Various forms of dementia, Alzheimer’s Disease (AD), are among the most common disorders in the elderly population [1]
In more detail, investigating a complexity measure of brain activity related to scale-free self-similarity of the signal dynamics–the EEG-derived Higuchi’s fractal dimension–we found that HFD increases from adolescence to adulthood and decreases from adulthood to old age
We found an association between reduced HFD and decreasing cognitive capacity as assessed by MMSE, in line with previous brain activity complexity studies [1,15]. These findings indicate that loss of neural efficiency and reduced cortical communication in AD [44] can be detected with the HFD measure, and provide further evidence strengthening that HFD is sensitive to progressing AD severity
Summary
Various forms of dementia, Alzheimer’s Disease (AD), are among the most common disorders in the elderly population [1]. A deeper understanding of the mechanisms involved in the development and progression of AD is critical for early diagnosis and effective treatment. The characteristic structural neuropathology of AD involves neuronal cell loss, neurofibrillary tangles and amyloid plaques [2]. On the functional neural level, profound changes in brain activity can be observed in AD patients. Slowing of brain activity is not selectively present in cognitive impaired or AD patients, but to a milder degree occurs during healthy aging [3,4,5]
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