engleski

Importance of non-cognitive symptoms in Alzheimer's disease

The current clinical criteria for diagnosis of AD are focused mostly on cognitive deficits produced by dysfunction of hippocampal, entorhinal and high-order neocortical areas (e.g. the Mini-Mental State Examination scores reflect mental state across exclusively cognitive domains), whereas noncognitive, behavioural and psychological symptoms of dementia (BPSD) such as disturbances in mood, emotion, appetite, and wake–sleep cycle, confusion, agitation and depression have been less considered. The early occurrence of these symptoms suggests brainstem involvement, and more specifically of the serotonergic nuclei. In spite of the fact that the Braak and Braak staging system (BBSS) and National Institutes of Aging – Reagan Institute (NIA-RI) neuropathological diagnostic criteria do not include their evaluation, several recent reports drew attention to the possibility of selective and early involvement of raphe nuclei, particularly the dorsal raphe nucleus (DRN), in the pathogenesis of AD (Šimić G. et al., Does Alzheimer's disease begin in the brainstem? Neuropathol. Appl. Neurobiol. 2009 ; 35: 532-554). From a number of standardized instruments that have been developed for the assessment of non-cognitive symptoms in dementia the following three are the most validated: the Neuropsychiatric Inventory (NPI), the AD Assessment Scale-Noncognitive portion (ADAS-noncog) and the Behavioral Pathology in AD Rating Scale (BEHAVE-AD). The NPI evaluates delusions, hallucinations, agitation, anxiety, dysphoria, euphoria, irritability, disinhibition, apathy, and aberrant motor behavior ; the ADAS-noncog covers a variety of behavioral symptoms, including tearfulness, depression, loss of concentration or increased distractibility, uncooperativeness, delusions, hallucinations, pacing, increased motor activity, tremor, and appetite changes, whereas the BEHAVE-AD focuses on paranoia and delusional ideation, hallucinations, activity disturbances, aggressiveness, diurnal rhythm disturbances, affective disturbances, and anxieties and phobias. Expanding our understanding of the raphe nuclei, particularly the DRN involvement in the early stages of AD to functional concepts beyond neuropathological descriptions, will likely have a strong impact on our understanding, detection and tracking of BPSD and AD progression, and on the development of new therapeutic strategies.

Alzheimer's disease; behavioral and psychological symptoms; beta-amyloid; cerebrospinal fluid; dorsal raphe nucleus; serotonin; tau protein

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