Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration

Elrod, Rachael; Peskind, Elaine R.; DiGiacomo, Lillian; Brodkin, Kayla I.; Veith, Richard C.; Raskind, Murray A.

doi:10.1176/ajp.154.1.25

Cited by 113 publications

(40 citation statements)

References 45 publications

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“…Noradrenergic function seems to be enhanced in older relative to young adults (Elrod et al, 1997; Raskind et al, 1999), which may mask the differences between both conditions (novel vs. standard) in this age group.…”

Section: Discussionmentioning

confidence: 98%

Effects of aging and involuntary capture of attention on event-related potentials associated with the processing of and the response to a target stimulus

Cid-Fernández

Lindı́n²,

Dı́az

2014

Front. Hum. Neurosci.

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The main aim of the present study was to assess whether aging modulates the effects of involuntary capture of attention by novel stimuli on performance, and on event-related potentials (ERPs) associated with target processing (N2b and P3b) and subsequent response processes (stimulus-locked Lateralized Readiness Potential -sLRP- and response-locked Lateralized Readiness Potential -rLRP-). An auditory-visual distraction-attention task was performed by 77 healthy participants, divided into three age groups (Young: 21–29, Middle-aged: 51–64, Old: 65–84 years old). Participants were asked to attend to visual stimuli and to ignore auditory stimuli. Aging was associated with slowed reaction times, target stimulus processing in working memory (WM, longer N2b and P3b latencies) and selection and preparation of the motor response (longer sLRP and earlier rLRP onset latencies). In the novel relative to the standard condition we observed, in the three age groups: (1) a distraction effect, reflected in a slowing of reaction times, of stimuli categorization in WM (longer P3b latency), and of motor response selection (longer sLRP onset latency); (2) a facilitation effect on response preparation (later rLRP onset latency), and (3) an increase in arousal (larger amplitudes of all ERPs evaluated, except for N2b amplitude in the Old group). A distraction effect on the stimulus evaluation processes (longer N2b latency) were also observed, but only in middle-aged and old participants, indicating that the attentional capture slows the stimulus evaluation in WM from early ages (from 50 years onwards, without differences between middle-age and older adults), but not in young adults.

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Section: Discussionmentioning

confidence: 98%

Effects of aging and involuntary capture of attention on event-related potentials associated with the processing of and the response to a target stimulus

Cid-Fernández

Lindı́n²,

Dı́az

2014

Front. Hum. Neurosci.

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“…On the other hand, a number of studies have shown no change in norepinephrine levels in different brain regions or cerebrospinal fluid (CSF) in both sporadic and familial AD cases (Sparks et al, 1988; Herregodts et al, 1989; Tohgi et al, 1992). In addition, increased norepinephrine levels were reported, which correlated with decreased cognitive function (Tohgi et al, 1992) and aging (Elrod et al, 1997) in AD patients.…”

Section: Noradrenergic Changes In Admentioning

confidence: 99%

Noradrenergic dysfunction in Alzheimer's disease

et al. 2015

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The brain noradrenergic system supplies the neurotransmitter norepinephrine throughout the brain via widespread efferent projections, and plays a pivotal role in modulating cognitive activities in the cortex. Profound noradrenergic degeneration in Alzheimer's disease (AD) patients has been observed for decades, with recent research suggesting that the locus coeruleus (where noradrenergic neurons are mainly located) is a predominant site where AD-related pathology begins. Mounting evidence indicates that the loss of noradrenergic innervation greatly exacerbates AD pathogenesis and progression, although the precise roles of noradrenergic components in AD pathogenesis remain unclear. The aim of this review is to summarize current findings on noradrenergic dysfunction in AD, as well as to point out deficiencies in our knowledge where more research is needed.

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“…Particularly interesting are studies in postmortem AD brains which identified compensatory mechanisms in surviving neurons of the LC network by means of upregulated synthesis of NE and/or a reduced reuptake of the neurotransmitter at the synaptic terminals [79]. This upregulation could explain the unexpected increase of NE levels in cerebrospinal fluid in AD patients with marked LC pathology [80,81]. …”

Section: Locus Coeruleus and The Norepinephrine Systemmentioning

confidence: 99%

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

Theofilas

Dunlop

Heinsen

et al. 2015

JAD

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Pharmacological interventions in Alzheimer's disease (AD) are likely to be more efficacious if administered early in the course of the disease, foregoing the spread of irreversible changes in the brain. Research findings underline an early vulnerability of the isodendritic core (IC) network to AD neurofibrillary lesions. The IC constitutes a phylogenetically conserved subcortical system including the locus coeruleus in pons, dorsal raphe nucleus and substantia nigra in the midbrain, and nucleus basalis of Meynert in basal forebrain. Through their ascending projections to the cortex, the IC neurons regulate homeostasis and behavior by synthesizing aminergic and cholinergic neurotransmitters. Here we reviewed the evidence demonstrating that neurons of the IC system show neurofibrillary tangles in the earliest stages of AD, prior to cortical pathology, and how this involvement may explain pre-amnestic symptoms, including depression, agitation and sleep disturbances in AD patients. In fact, clinical and animal studies show a significant reduction of AD cognitive and behavioral symptoms following replenishment of neurotransmitters associated with the IC network. Therefore, the IC network represents a unique candidate for viable therapeutic intervention and should become a high priority for research in AD.

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Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration

Cited by 113 publications

References 45 publications

Effects of aging and involuntary capture of attention on event-related potentials associated with the processing of and the response to a target stimulus

Effects of aging and involuntary capture of attention on event-related potentials associated with the processing of and the response to a target stimulus

Noradrenergic dysfunction in Alzheimer's disease

Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer’s Disease Pathogenesis

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