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PubMed1997

Early neuropathologic effects of mild or moderate hypoxemia after controlled cortical impact injury in rats.

Hypoxemia has detrimental effects after traumatic brain injury (TBI) in both experimental models and humans. The purpose of this study was to determine the effect of mild or moderate hypoxemia on early histologic and motor functional outcome after controlled cortical impact (CCI) in rats. Anesthetized rats underwent CCI and were randomized to receive mild (FiO2 = 13%, n = 6), moderate (FiO2 = 11%, n = 9), or no (FiO2 = 33%, n = 6) hypoxemia for 30 min after trauma. Sham-operated rats without hypoxemia (n = 7) were used as controls. Motor function (beam balance latency) was assessed on days 0-5. Rats were killed 7 days after injury and their brains removed for assessment of survival of hippocampal neurons and contusion volume. Terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats killed at 6, 24, and 72 h after CCI and moderate hypoxemia to assess DNA fragmentation in situ. Mild and moderate hypoxemia augmented motor function deficits after CCI in a dose-dependent manner. Moderate hypoxemia after CCI reduced 7-day survival of CA3 neurons but not CA1 neurons vs. sham (55 [46-86] vs. 99 [95-130], p < 0.05, and 79 [63-86] vs. 101 [81-123], NS, respectively; % uninjured hemisphere, median [range]). The addition of mild or moderate hypoxemia did not increase contusion volume. TUNEL-positive neurons were seen in ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after trauma, and in ipsilateral CA3 hippocampal neurons and thalamus at 24 and 72 h. Moderate hypoxemia augments CA3 neuronal death and early motor functional deficits after CCI. The pattern of DNA fragmentation in selectively vulnerable neurons suggests that apoptosis may play a role in the delayed neuronal death seen after TBI.

Analysis of Variance↗

PubMed1994

Benchmark test of neutron transport calculations: indium, nickel, gold, europium, and cobalt activation with and without energy moderated fission neutrons by iron simulating the Hiroshima atomic bomb casing.

A benchmark test of the Monte Carlo neutron and photon transport code system (MCNP) was performed using a bare- and energy-moderated 252Cf fission neutron source which was obtained by transmission through 10-cm-thick iron. An iron plate was used to simulate the effect of the Hiroshima atomic bomb casing. This test includes the activation of indium and nickel for fast neutrons and gold, europium, and cobalt for thermal and epithermal neutrons, which were inserted in the moderators. The latter two activations are also to validate 152Eu and 60Co activity data obtained from the atomic bomb-exposed specimens collected at Hiroshima and Nagasaki, Japan. The neutron moderators used were Lucite and Nylon 6 and the total thickness of each moderator was 60 cm or 65 cm. Measured activity data (reaction yield) of the neutron-irradiated detectors in these moderators decreased to about 1/1,000th or 1/10,000th, which corresponds to about 1,500 m ground distance from the hypocenter in Hiroshima. For all of the indium, nickel, and gold activity data, the measured and calculated values agreed within 25%, and the corresponding values for europium and cobalt were within 40%. From this study, the MCNP code was found to be accurate enough for the bare- and energy-moderated 252Cf neutron activation calculations of these elements using moderators containing hydrogen, carbon, nitrogen, and oxygen.

Cobalt↗

PubMed2001

Moderate-intensity muscle pain can be produced and sustained during cycle ergometry.

PURPOSE: The aim of this experiment was to determine whether moderate-intensity quadriceps muscle pain could be produced and sustained during cycle ergometry. METHODS: 12 women volunteers completed a peak cycle ergometry test during which quadriceps muscle pain-intensity ratings were obtained using a 0-10 scale. On a subsequent day, participants cycled for 20 min beginning at the power output associated with quadriceps muscle pain threshold during the peak test. Participants manipulated power output during the first 10 s of each minute to produce and sustain moderate-intensity quadriceps muscle pain. During the last 20 s of each minute, VO2, ratings of quadriceps muscle pain intensity, and ratings of perceived exertion (Borg 6-20) were obtained. RESULTS: Moderate-intensity quadriceps pain ratings were achieved within 4 min, during which time the average power output was increased from 124 to 138 W. Pain-intensity ratings were unchanged from minutes 4 to 20 (F = 0.94; df = 16, 176; P = 0.52; eta2 = 0.079). Quadriceps RPE responses mimicked the pain responses. To sustain a moderate-intensity quadriceps pain participants reduced power output significantly (F = 7.75; df = 16, 176; P < 0.001; eta2 = 0.413) and in a linear fashion by 21.7 W (15.7%). The changes in % VO2peak were similar in pattern to the changes in power output but smaller in magnitude. CONCLUSIONS: 1) College women can produce and sustain a moderate-intensity quadriceps muscle pain during cycle ergometry, 2) moderate-intensity quadriceps muscle pain is sustained by reducing power output, and 3) sustaining moderate-intensity quadriceps muscle pain during short duration cycling is associated with a "hard" perceptual effort and 69-74% VO2peak.

Adult↗

PubMedDate not supplied

Moderators of an uncertainty management intervention: for men with localized prostate cancer.

BACKGROUND: The effectiveness of psycho-educational interventions for cancer patients is well documented, but less is known about moderating characteristics that determine which subgroups of patients are most likely to benefit. OBJECTIVES: The aim of this study was to determine whether certain individual characteristics of African-American and White men with localized prostate cancer moderated the effects of a psycho-educational Uncertainty Management Intervention on the outcomes of cancer knowledge and patient-provider communication METHODS: Men were blocked by ethnicity and randomly assigned to one of three conditions: Uncertainty Management Intervention provided to the patient only, Uncertainty Management Intervention supplemented by delivery to the patient and family member, or usual care. The individual characteristics explored were education, sources for information, and intrinsic and extrinsic religiosity. RESULTS: Using repeated measures multivariate analysis of variance, findings indicated that there were no significant moderator effects for intrinsic religiosity on any of the outcomes. Lower level of education was a significant moderator for improvement in cancer knowledge. For the outcome of patient-provider communication, fewer sources for cancer information was a significant moderator for the amount told the patient by the nurse and other staff. Less extrinsic religiosity was a significant moderator for three areas of patient provider communication. The three areas are the amount (a) the physician tells the patient; (b) the patient helps with planning treatment; and (c) the patient tells the physician. CONCLUSIONS: Testing for moderator effects provides important information regarding beneficiaries of interventions. In the current study, men's levels of education, amount of sources for information, and extrinsic religiosity influenced the efficacy of the Uncertainty Management Intervention on important outcomes.

Black or African American↗

PubMed2003

Alcohol choice and amphetamine effects in light and moderate drinkers.

BACKGROUND: The results of previously published reports suggest that light and moderate drinkers respond differently to the effects of commonly abused sedatives (e.g., diazepam or ethanol). The purpose of this experiment was to determine whether light and moderate drinkers respond differentially to the effects of ethanol and d-amphetamine. METHODS: In the first phase of this experiment, volunteers (eight light drinkers and eight moderate drinkers) randomly sampled 0.5 g/kg of ethanol and placebo across two separate sessions. In the second phase, volunteers completed three sessions in which they chose either ethanol or placebo. In the third phase, volunteers received 0, 5, 10, and 15 mg of d-amphetamine. Each dose was tested twice. After drug administration in each phase, volunteers completed a battery of subject-rated, performance, and physiologic measures periodically for 5 hr. RESULTS: Ethanol produced prototypical subject-rated effects (e.g., increased ratings on the Alcohol Sensation Scale), but it was chosen over placebo infrequently. Light and moderate drinkers did not differ in terms of the self-reported or reinforcing effects of ethanol. d-Amphetamine produced prototypical subject-rated stimulant-like effects (e.g., dose-dependent increases in ratings of High and Rush). Moderate drinkers reported significantly greater drug effects than light drinkers. Responses to ethanol reliably predicted subsequent responses to d-amphetamine on several measures. CONCLUSIONS: The results of this experiment suggest that even moderate ethanol use may increase an individual's vulnerability to abuse drugs. Future studies should determine whether light and moderate drinkers respond differentially to other commonly abused drugs (e.g., opioids) and whether behavioral responses to ethanol also predict responses to these compounds.

Adult↗

PubMed2005

The diagnosis and characteristics of moderate dry eye in non-contact lens wearers.

PURPOSE: To identify and characterize moderate dry eye in non-contact lens wearers with a new scoring system-based dry eye questionnaire and to determine which objective tests better differentiate patients with moderate dry eye from healthy patients. METHODS: Fifty-two healthy subjects (21 women and 31 men with a mean age of 27.8 +/- 9.2 years) and 37 subjects with moderate dry eye (33 women and 4 men with a mean age of 36.4 +/- 12.9 years) completed a 42-item dry eye questionnaire. Seventeen healthy subjects (11 women and 6 men with a mean age of 30.5 +/- 9.7 years) and 28 subjects with moderate dry eye (24 women and 4 men with a mean age of 38.50 +/- 3.8 years) underwent additional objective assessment of ocular surface health, tear osmolality, tear stability, and tear volume. RESULTS: Subjects with moderate dry eye scored significantly higher (49.8 +/- 20.3, P<0.0001) on the dry eye questionnaire than did normal subjects (11.7 +/- 10.3). Ocular irritation symptoms worsened with progression of time of day in both groups of subjects. Internal reliability (0.95 Cronbach alpha) was excellent, and concurrent validity (Spearman rho 0.507) was acceptable when compared to the McMonnies and Ho dry eye questionnaire. Significant differences in tear osmolality (P<0.00001), invasive tear breakup time (P<0.034), and corneal vital dye staining (P<0.0001) were detected between the two groups of subjects. A stepwise linear regression on objective clinical tests, however, did not account for 77% of the total variance in the questionnaire scores. CONCLUSIONS: A unique scoring system-based dry eye questionnaire was validated to separate non-contact lens wearers with moderate dry eye from healthy subjects. Objective tests of tear osmolality and stability and ocular surface integrity were better than other clinical measures at identifying differences between the two subject groups. The results strongly support the evidence that the diagnosis and treatment of moderate dry eye requires a detailed assessment of self-perceived symptoms and that objective clinical testing alone may be insufficient.

Adolescent↗

PubMed1996

Comparison of proliferative activities and metastases between two subtypes classified at the deeply infiltrating sites of colorectal moderately differentiated adenocarcinomas.

Twenty-eight moderately differentiated adenocarcinomas invading beyond the muscularis propria of the colorectum were subclassified as 13 moderate- and 15 poor-subtype tumors based on the histology at the deeply infiltrating sites. Moderately differentiated cancer cells were correlated with liver metastasis and p53 immunoreactivity. Poorly differentiated cancer cells were correlated with lymph node metastases but not to p53 immunoreactivity. The proliferative cell nuclear antigen (PCNA) labeling index (LI), Ki-67 LI and agyrophilic nuclear organizer regions (AgNOR) values determined for the poorly differentiated cancer cells in the poor-subtype tumors were significantly lower than those of moderately differentiated cancer cells in the moderate-subtype tumors. In cells from tumors classified as poor-subtype, poor differentiation was associated with decreased PCNA LI levels, but with unchanged Ki-67 LI and AgNOR values. These results indicate that colorectal adenocarcinoma cells that are histologically subclassified as moderately differentiated have different proliferative and metastatic activities from cancer cells that are poorly differentiated. Moderately differentiated cancer cells are associated with hematogenous metastasis to liver and high proliferative activity, and loss of tubular formation of cancer cells may be fundamentally related to lymph node metastasis and infiltrative growth.

Adenocarcinoma↗

PubMed1999

Very and moderate preterm births: are the risk factors different?

OBJECTIVE: To describe the risk factors for very preterm births and to compare the strengths of the associations between these risk factors and very and moderate preterm births. DESIGN: A case-control study. SETTING: Fifteen European countries. METHODS: Between 1994 and 1997, 1675 very preterm births, 3652 moderate preterm births and an unmatched control group of 7965 births at term were included. Odds ratios for very and moderate preterm births (related to socioeconomic status, behavioural factors, maternal age, body mass index and obstetric history) were estimated and compared using polytomous logistic regression. RESULTS: Underprivileged social situation, older maternal age and adverse previous pregnancy outcomes were significantly related to very and moderate preterm births. However, these factors were more strongly associated with very preterm births than with moderate preterm births, for both spontaneous and induced deliveries. Smoking during pregnancy, young maternal age and low body mass index were significantly related to very and moderate spontaneous preterm births, but no significant difference in odds ratios was observed between the two outcomes. CONCLUSION: These results suggest that risk factors for very and moderate preterm births are similar, but the strength of the associations differ, especially for social factors and obstetric history.

Adult↗

PubMed1996

Defective thrombin-induced calcium changes and aggregation of Bernard-Soulier platelets are not associated with deficient moderate-affinity receptors.

Cloning of the moderate-affinity, serpentine thrombin receptor has helped clarify the mechanism of thrombin-induced platelet activation. Proteolytic cleavage by thrombin generates a new amino terminal that autostimulates the receptor, leading to activation of multiple signaling pathways and the platelet response. The function of other thrombin receptors, such as high-affinity glycoprotein Ib (GPIb), on platelets and their relationships to the moderate-affinity receptor remain unclear. The present study examined the role of the moderate-affinity thrombin receptor in Bernard-Soulier syndrome (BSS) platelets, which contain low amounts of GPIb. Platelets from four BSS subjects displayed normal aggregation profiles and cytosolic calcium changes in response to moderate or high concentrations of thrombin. In contrast, the BSS platelet aggregation response was delayed and calcium changes were absent in response to low thrombin concentrations. Platelets from an asymptomatic BSS heterozygote displayed an activation profile similar to those of control individuals. Specific activation of the moderate-affinity receptor by a synthetic peptide caused similar aggregation in platelets from all individuals. The synthetic peptide also elicited calcium responses in BSS platelets. Platelets from the BSS subjects and from an individual with the May-Hegglin anomaly showed increased expression of the moderate-affinity thrombin receptor by flow-cytometric analyses. These results suggest that BSS platelets possess high levels of a functional moderate-affinity thrombin receptor, probably due to large platelet size, and provide indirect evidence that a high-affinity thrombin receptor is associated with GPIb.

Bernard-Soulier Syndrome↗

PubMed1998

Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction.

BACKGROUND AND PURPOSE: Animal research and clinical studies in head trauma patients suggest that moderate hypothermia may improve outcome by attenuating the deleterious metabolic processes in neuronal injury. Clinical studies on moderate hypothermia in the treatment of acute ischemic stroke patients are still lacking. METHODS: Moderate hypothermia was induced in 25 patients with severe ischemic stroke in the middle cerebral artery (MCA) territory for therapy of postischemic brain edema. Hypothermia was induced within 14+/-7 hours after stroke onset and achieved by external cooling with cooling blankets, cold infusions, and cold washing. Patients were kept at 33 degreesC body-core temperature for 48 to 72 hours, and intracranial pressure (ICP), cerebral perfusion pressure, and brain temperature were monitored continuously. Outcome at 4 weeks and 3 months after the stroke was analyzed with the Scandinavian Stroke Scale (SSS) and Barthel index. The side effects of induced moderate hypothermia were analyzed. RESULTS: Fourteen patients survived the hemispheric stroke (56%). Neurological outcome according to the SSS score was 29 (range, 25 to 37) 4 weeks after stroke and 38 (range 28 to 48) 3 months after stroke. During hypothermia, elevated ICP values could be significantly reduced. Herniation caused by a secondary rise in ICP after rewarming was the cause of death in all remaining patients. The most frequent complication of moderate hypothermia was pneumonia in 10 of the 25 patients (40%). Other severe side effects of hypothermia could not be detected. CONCLUSIONS: Moderate hypothermia in the treatment of severe cerebral ischemia is not associated with severe side effects. Moderate hypothermia can help to control critically elevated ICP values in severe space-occupying edema after MCA stroke and may improve clinical outcome in these patients.

Adult↗

PubMed2006

Impact of moderate functional mitral insufficiency in patients undergoing surgical revascularization.

BACKGROUND: Mild and moderate functional ischemic mitral insufficiency present at the time of surgical revascularization present clinical uncertainty. It is unclear whether the relatively poor outcomes in this cohort are dependent on valvular function or related to left ventricular dysfunction. The purpose of this study was to examine the early and late outcomes in patients with less-than-severe functional ischemic mitral insufficiency at the time of isolated coronary artery bypass grafting (CABG). METHODS AND RESULTS: From 1996 through 2004, 2242 consecutive patients undergoing isolated CABG were identified as having none to moderate mitral regurgitation (MR) and no valve leaflet pathology. All of the patients at this single institution routinely had an intraoperative transesophageal echocardiography, prospectively quantified MR, and ejection fraction (EF). The New York State Cardiac Surgery Reporting System infrastructure was used to prospectively collect in-hospital patient variables and outcomes. Social Security Death Benefit Index was used to determine long-term survival. Odds ratio and significance (P value) are presented for each determined risk factor. There were 841 patients (37.5%) with no MR, 1137 (50.7%) with mild MR, and 264 (11.8%) with moderate MR. The patients with moderate MR were more likely to be older, female, and have more renal disease, previous MI, congestive heart failure, previous cardiac surgery, and lower EFs. Hospital mortality was independently and significantly associated with renal disease, decreasing EF, increasing age, previous cardiac operation, and cerebral vascular disease. Multivariable analysis revealed decreased survival with increasing age, previous operation, congestive heart failure, diabetes, nonelective operation, decreasing EF, and the presence of moderate MR (expbeta = 1.49; P=0.007) and mild MR (expbeta = 1.34; P=0.033). CONCLUSIONS: Independent of ventricular function, mild and moderate functional mitral insufficiency are associated with significantly decreased survival in patients undergoing CABG. Whether correction of moderate functional MR at the time of CABG improves outcome still needs to be determined.

Aged↗

PubMed2003

Clinical and biological heterogeneity in children with moderate asthma.

To evaluate the relationship between inflammatory markers and severity of asthma in children, the amount of interleukin-8 (IL-8) and granulocyte/macrophage colony-stimulating factor (GM-CSF) released by peripheral blood mononuclear cells, exhaled nitric oxide (FE NO) levels, p65 nuclear factor-kappaB subunit, and phosphorylated IkBalpha expression by peripheral blood mononuclear cells were assessed in six control subjects, 12 steroid-naives subjects with intermittent asthma, and 17 children with moderate asthma. To investigate their predictive value, biomarker levels were correlated with the number of exacerbations during a 18-month follow-up period. We found that GM-CSF release was higher in moderate and intermittent asthmatics than in control subjects, whereas IL-8 release was higher in moderate than in intermittent asthmatics and control subjects. FE NO levels were similar among study groups. In moderate asthmatics, IL-8, GM-CSF, and FE NO significantly correlated with the exacerbation numbers. Moreover, p65 and phosphorylated IkBalpha levels were greater in moderate than in intermittent asthmatics and control subjects. According to GM-CSF, IL-8, and FE NO levels, two distinct subgroups of moderate asthmatics (low and high producers) were identified. High producers experienced more exacerbations than low producers. This study shows ongoing inflammation associated with biological and clinical heterogeneity in moderate asthmatics despite regular treatment and proposes that large prospective studies confirm the importance of biomarkers to assess inflammation and asthma control in children with asthma.

Adolescent↗

PubMed2003

Mediator of moderators: temporal stability of intention and the intention-behavior relation.

Intention certainty, past behavior, self-schema, anticipated regret, and attitudinal versus normative control all have been found to moderate intention-behavior relations. It is argued that moderation occurs because these variables produce "strong" intentions. Stability of intention over time is a key index of intention strength. Consequently, it was hypothesized that temporal stability of intention would mediate moderation by these other moderators. Participants (N = 185) completed questionnaire measures of theory of planned behavior constructs and moderator variables at two time points and subsequently reported their exercise behavior. Findings showed that all of the moderators, including temporal stability, were associated with significant improvements in consistency between intention and behavior. Temporal stability also mediated the effects of the other moderators, supporting the study hypothesis.

Humans↗

PubMed2004

Moderation of cognition-intention and cognition-behaviour relations: a meta-analysis of properties of variables from the theory of planned behaviour.

Meta-analysis was used to quantify the moderating effects of seven properties of cognitions-accessibility, temporal stability, direct experience, involvement, certainty, ambivalence and affective-cognitive consistency-on cognition-intention and cognition-behaviour relations. Literature searches revealed 44 studies that could be included in the review. Findings showed that all of the properties, except involvement, moderated attitude-behaviour consistency. Similarly, all relevant moderators improved the consistency between intentions and behaviour. Temporal stability moderated PBC-behaviour relations, certainty moderated subjective norm-intention relations, and ambivalence, certainty, and involvement all moderated attitude-intention relations. Overall, temporal stability appeared to be the strongest moderator of cognition-behaviour relations.

Affect↗

PubMed2005

Effect of moderate-intensity exercise, whole-body periodic acceleration, and passive cycling on nitric oxide release into circulation.

STUDY OBJECTIVE: To determine if a 3-min bout of moderately intensive supine bicycle exercise, whole-body periodic acceleration (pGz), and passive motorized cycling cause nitric oxide (NO) release into the circulation, as detected by dicrotic notch descent on the diastolic limb of a finger pulse wave. PARTICIPANTS: Fourteen healthy adults underwent two levels of supine bicycle ergometry that caused heart rate to rise to 56% (light moderate exercise) and 67% (heavy moderate exercise) of maximum predicted heart rate, and a single bout of pGz. Several months later, 9 of the 14 subjects underwent passive motorized cycling. METHODS: The ECG and finger pulse wave were recorded. The dicrotic notch position was computed from the amplitude of the digital pulse wave (a) divided by the height of the dicrotic notch above the end-diastolic level (b) and designated the a/b ratio. Increase of the a/b ratio due to dicrotic notch descent reflects the vasodilator action of NO on resistance vessels. The last 30 s of baseline, exercise or pGz, and recovery periods were analyzed. RESULTS: Compared to baseline, light moderate exercise produced a nonsignificant rise of the a/b ratio. Both heavy moderate exercise and pGz produced statistically significant rises of peak and mean a/b ratios over baseline. Heavy moderate exercise produced a greater mean a/b ratio than pGz, but the peak a/b ratio did not differ between the two. Episodic rises and falls of a/b ratios were more common during pGz than exercise. Passive motorized cycling did not alter the a/b ratio. CONCLUSIONS: Dicrotic notch descent occurs during a brief bout of moderate cycling exercise, consistent with NO release into circulation. pGz produces comparable descent, but passive motorized cycling does not. In terms of the beneficial effects of NO, this suggests that pGz might serve as a substitute in subjects who are physically incapable of exercising.

Adult↗

PubMed1994

The effect of moderate alcohol use on the relationship between stress and depression.

OBJECTIVES: The purpose of the study was to determine whether moderate alcohol use mediates or buffers the effect of stress on depression in a group of non-Hispanic White men and women. METHODS: Data are from the Los Angeles Epidemiological Catchment Area cohort. Individuals were assessed at two time periods, 1 year apart. Mean depression scores were analyzed for each level of stress and alcohol use. RESULTS: In the simultaneous presence of both chronic strain and negative life events, a U-shaped pattern was observed in which abstainers and light and heavy drinkers had higher depression scores at the second time period than did light-moderate and moderate alcohol users. The U-shaped relationship remained when the effects of sex, age, and physical health status were controlled. CONCLUSIONS: Light-moderate and moderate drinkers had less depression in the presence of stress than persons in other more extreme drinking categories. Moderate alcohol use may serve as a proxy for a spectrum of generally moderate behaviors that either attenuate the effect of stress on depression or suppress the effects of stress.

Adult↗

PubMed1998

Profitability of moderate intensive grazing of diary cows in the northeast.

Empirical analysis of the profitability of moderate grazing are presented based on sample dairy farms in Pennsylvania and New York. Net income per cow was higher for dairy farms that employed moderate intensive grazing than for dairy farms that employed extensive grazing. Income appeared to be adequate for family living expenses, but moderate intensive grazing could not be considered a high profit system. Detailed analyses of dairy farms that employed moderate and extensive grazing in northern Pennsylvania indicated that returns to management and owner equity were higher for pasture enterprises than for corn silage or hay enterprises. Positive dairy profits were related to lower feed costs. Milk production was lower on farms that employed moderate grazing than on farms that employed extensive grazing. Logit regression analysis characterized farms that employed moderate intensive grazing as oriented toward dairy rather than toward crop production; these farms had lower culling rates and a greater dependence on milk sales as a share of total sales. The reduced use of fertilizers and chemicals suggests that moderate grazing had environmentally sustainable features.

Animal Feed↗

PubMed2006

A systematic review of assessment and treatment of moderate to severe Alzheimer's disease.

OBJECTIVE: The systematic, large-scale study of therapies for moderate to severe Alzheimer's disease (AD) is a relatively recent advancement in the field. This review describes for the general practitioner the characterization of moderate to severe AD, discusses the development of metrics sensitive to the constellation of symptoms in these patients, and critically evaluates the use of those measures in moderate to severe AD clinical trials. DATA SOURCES: Published clinical trials obtained by MEDLINE searches used the following key words: moderate AD, severe AD, donepezil, rivastigmine, galantamine, memantine, and anti-dementia agents. Clinical trials were limited by language (English), study type (clinical trial), and publication dates (1990-2005). STUDY SELECTION: Nine clinical trials comprise the studies conducted to date in moderate to severe AD and include 5 prospective randomized clinical trials (3 for memantine, 2 for donepezil) and 4 retrospective subanalyses (2 for galantamine, 2 for rivastigmine) of primary datasets. DATA EXTRACTION: Clinical trials are summarized and major findings are reviewed. DATA SYNTHESIS: The data reviewed support the decision to initiate and maintain treatment in moderate to severe AD patients. CONCLUSIONS: The development and implementation of improved metrics for moderate to severe AD patients has revealed that meaningful benefits are attainable in this patient population by treatment with the N-methyl-D-aspartate receptor antagonist memantine. Evidence also indicates a benefit from cholinesterase inhibitor treatment, although further study of these agents in this patient population is warranted.

Journal Article↗