Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults

ObjectiveTo assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults.DesignTwo-year prospective, observational study.Setting and ParticipantsThe study included 405 adults aged 65–84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan.MethodsParticipants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores.ResultsAmong individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02–0.62; p = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13–0.60; p < 0.001).Conclusion and ImplicationsHigher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults

Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders”

Given the relationship between anticholinergic activity (AA) and Alzheimer’s disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh

Association Between Serum Anticholinergic Activity and Psychiatric Symptoms of Chronic Schizophrenia

The cholinergic system in schizophrenia has been associated with treatments, adverse effects, and pathophysiological processes. Although the role of the cholinergic system in schizophrenia has been thoroughly investigated, few studies have examined the dynamics of human cholinergic systems in vivo. We compared serum anticholinergic activity (SAA) in patients with schizophrenia to that in healthy controls and investigated correlations between anticholinergic activity and various domains of psychiatric symptoms. Fifteen chronically medicated patients with schizophrenia and 10 healthy controls participated in the study. We measured SAA using a receptor-binding assay ([3H]-QNB). We also measured extrapyramidal motor symptoms and psychiatric symptoms, and assessed cognitive functioning with subscales of the Wechsler Memory Scale. Elevated levels of SAA (>1.95pmol/ml) were significantly more common among patients with schizophrenia than among healthy controls (P<0.001). There was a significant negative correlation between SAA and extrapyramidal motor symptoms in patients with schizophrenia (P=0.043). We found no significant association between SAA and other psychiatric symptoms and cognitive functions. These results indicate that SAA is greater among patients with schizophrenia than healthy controls, and that the anticholinergic effects might reduce extrapyramidal motor symptoms but exacerbate thought disorders. Further studies are warranted to confirm this finding in a larger cohort of non-medicated patients

Serum Anticholinergic Activity: A Possible Peripheral Marker of the Anticholinergic Burden in the Central Nervous System in Alzheimer’s Disease

We review the utility of serum anticholinergic activity (SAA) as a peripheral marker of anticholinergic activity (AA) in the central nervous system (CAA). We hypothesize that the compensatory mechanisms of the cholinergic system do not contribute to SAA if their system is intact and that if central cholinergic system deteriorates alone in conditions such as Alzheimer’s disease or Lewy body dementia, CAA and SAA are caused by way of hyperactivity of inflammatory system and SAA is a marker of the anticholinergic burden in CNS. Taking into account the diurnal variations in the plasma levels of corticosteroids, which are thought to affect SAA, it should be measured at noon or just afterward