Staging Neurodegenerative Disorders: Structural, Regional, Biomarker, and Functional Progressions

Abstract

The notion of staging in the neurodegenerative disorders is modulated by the constant and progressive loss of several aspects of brain structural integrity, circuitry, and neuronal processes. These destructive processes eventually remove individuals' abilities to perform at sufficient and necessary functional capacity at several levels of disease severity. The classification of (a) patients on the basis of diagnosis, risk prognosis, and intervention outcome, forms the basis of clinical staging, and (b) laboratory animals on the basis of animal model of brain disorder, extent of insult, and dysfunctional expression, provides the components for the clinical staging and preclinical staging, respectively, expressing associated epidemiological, biological, and genetic characteristics. The major focus of clinical staging in the present account stems from the fundamental notions of Braak staging as they describe the course and eventual prognosis for Alzheimer's disease, Lewy Body dementia, and Parkinson's disease. Mild cognitive impairment, which expresses the decline in episodic and semantic memory performance below the age-adjusted normal range without marked loss of global cognition or activities of daily living, and the applications of longitudinal magnetic resonance imaging, major instruments for the monitoring of either disease progression in dementia, present important challenges for staging concepts. Although Braak notions present the essential basis for further developments, current staging conceptualizations seem inadequate to comply with the massive influx of information dealing with neurodegenerative processes in brain, advanced both under clinical realities, and discoveries in the laboratory setting. The contributions of various biomarkers of disease progression, e.g., amyloid precursor protein, and neurotransmitter system imbalances, e.g., dopamine receptor supersensitivity and interactive propensities, await their incorporation into the existing staging models thereby underlining the ongoing, dynamic feature of the staging of brain disorders.

Cognitive Performance Deficits and Dysgraphia in Alzheimer’s Disease Patients

“…These findings imply that assessment of dysgraphia ought to contribute an additional diagnostic assessment that provides evidence of compromised functioning in motor, cognitive and emotional domains.The loss of functional integrity in these AD patients was serious; nevertheless, the manifest benefits arising from a motor interventional set-up, e.g. physical exercise programs, for these patients ought not to be rejected outright [58].…”

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

“…Although Braak notions and revised criteria present the essential basis for further developments, current staging conceptualizations seem inadequate to comply with the progress on the field [72]. For example, the contributions of various biomarkers of disease progression, such as Aβ, and neurotransmitter system imbalances, e.g., dopamine receptor supersensitivity and interactive propensities, as well as CART, await their incorporation into the existing staging models thereby underlining the ongoing, dynamic feature of the staging of the brain disorder, it is probably more valuable for the early diagnosis.…”

The effect of exercise intervention on cognitive performance in persons at risk of, or with, dementia: A systematic review and meta-analysis

“…The functional and cognitive attributes affected by the deterioration of these brain structures include learning, memory, attention, motivation, executive function, motor function, global cognition, and activities during daily living [5,7]. MCI, which is often a prelude to dementia [8,9], is also associated with disproportionate atrophy in the medial temporal and temporal cortices [6,7].…”

“…MCI, which is often a prelude to dementia [8,9], is also associated with disproportionate atrophy in the medial temporal and temporal cortices [6,7]. The severity and extent of dementia-related atrophy increase as a function of time, destroying cognitive and functional abilities at each stage.…”