Characterization of Balance Control and Postural Stability in Patients With Alzheimer Disease.

Balance in Alzheimer disease (AD) patients is not rigorously understood. In this study, we characterize balance using qualitative [Berg Balance Scale (BBS)] and quantitative measures (posturography) and assess relationships between qualitative and quantitative balance measures in AD. Patients with mild-moderate AD (n=48) were recruited. BBS scores and posturography metrics, including medial-lateral sway range, anterior-posterior sway range, sway area, and sway velocity, were assessed in eyes-open and eyes-closed conditions. Adjusted linear regressions were used to assess relationships between posturography and BBS score. Mean BBS score was 50.4±5.3. In eyes-open conditions, posturography and BBS score were not significantly associated. In eyes-closed conditions, better BBS score was significantly associated with lower sway area (ß=-0.91; P =0.006). Better scores of BBS items involving turning and reduced base of support were associated with greater eyes-closed sway area. Posturography in the more challenging eyes-closed condition may predict functional balance deficits in AD patients.

Vestibular Function Predicts Balance and Fall Risk in Patients with Alzheimer's Disease.

BACKGROUND: Patients with Alzheimer's disease (AD) are at high risk for falls. Vestibular dysfunction predicts balance impairment in healthy adults; however, its contribution to falls in patients with AD is not well known. OBJECTIVE: The objective of this study was to assess whether vestibular function contributes to balance and fall risk in patients with AD. METHODS: In this prospective observational study, we assessed vestibular function using measures of semicircular canal (vestibulo-ocular reflex (VOR) gain) and saccular function (cervical vestibular-evoked myogenic (cVEMP) response), and we assessed balance function using the Berg Balance Scale and quantitative posturography. We evaluated falls incidence for a mean 1-year follow-up period (range 3-21 months) in 48 patients with mild-moderate AD. RESULTS: Relative to matched controls, AD patients exhibited increased medio-lateral (ML) sway in eyes-open (0.89 cm versus 0.69 cm; p = 0.033) and eyes-closed (0.86 cm versus 0.65 cm; p = 0.042) conditions. Among AD patients, better semicircular canal function was associated with lower ML sway and antero-posterior (AP) sway in the eyes-closed condition (ß= -2.42, 95% CI (-3.89, -0.95), p = 0.002; ß= -2.38, 95% CI (-4.43, -0.32), p = 0.025, respectively). Additionally, better saccular function was associated with lower sway velocity (ß= -0.18, 95% CI (-0.28, -0.08); p = 0.001). Finally, we observed that better semicircular canal function was significantly associated with lower likelihood of falls when adjusted for age, sex, and MMSE score (HR = 0.65; p = 0.009). CONCLUSION: These results support the vestibular system as an important contributor to balance and fall risk in AD patients and suggest a role for vestibular therapy.

A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine.

OBJECTIVE: To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine. METHODS: This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced ≥2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. RESULTS: Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. CONCLUSIONS: This study supports that ketorolac NS is superior to placebo and that it is non-inferior to sumatriptan NS for the acute abortive treatment of migraine.

Interictal, circulating sphingolipids in women with episodic migraine: A case-control study.

OBJECTIVE: To evaluate interictal, circulating sphingolipids in women migraineurs. METHODS: In the fasting state, serum samples were obtained pain-free from 88 women with episodic migraine (EM; n=52) and from controls (n=36). Sphingolipids were detected and quantified by high-performance liquid chromatography coupled with tandem mass spectrometry using multiple reaction monitoring. Multivariate logistic regression was used to examine the association between serum sphingolipids and EM odds. A recursive partitioning decision tree based on the serum concentrations of 10 sphingolipids was used to determine the presence or absence of EM in a subset of participants. RESULTS: Total ceramide (EM 6,502.9 ng/mL vs controls 10,518.5 ng/mL; p<0.0001) and dihydroceramide (EM 39.3 ng/mL vs controls 63.1 ng/mL; p<0.0001) levels were decreased in those with EM as compared with controls. Using multivariate logistic regression, each SD increase in total ceramide (odds ratio [OR] 0.07; 95% confidence interval [CI]: 0.02, 0.22; p<0.001) and total dihydroceramide (OR 0.05; 95% CI: 0.01, 0.21; p<0.001) levels was associated with more than 92% reduced odds of migraine. Although crude sphingomyelin levels were not different in EM compared with controls, after adjustments, every SD increase in the sphingomyelin species C18:0 (OR 4.28; 95% CI: 1.87, 9.81; p=0.001) and C18:1 (OR 2.93; 95% CI: 1.55, 5.54; p=0.001) was associated with an increased odds of migraine. Recursive portioning models correctly classified 14 of 14 randomly selected participants as EM or control. CONCLUSION: These results suggest that sphingolipid metabolism is altered in women with EM and that serum sphingolipid panels may have potential to differentiate EM presence or absence. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that serum sphingolipid panels accurately distinguish women with migraine from women without migraine.

Ictal adipokines are associated with pain severity and treatment response in episodic migraine.

OBJECTIVE: To evaluate ictal adipokine levels in episodic migraineurs and their association with pain severity and treatment response. METHODS: This was a double-blind, placebo-controlled trial evaluating peripheral blood specimens from episodic migraineurs at acute pain onset and 30 to 120 minutes after treatment with sumatriptan/naproxen sodium vs placebo. Total adiponectin (T-ADP), ADP multimers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]), leptin, and resistin levels were evaluated by immunoassays. RESULTS: Thirty-four participants (17 responders, 17 nonresponders) were included. In all participants, pretreatment pain severity increased with every quartile increase in both the HMW:T-ADP ratio (coefficient of variation [CV] 0.51; 95% confidence interval [CI]: 0.08, 0.93; p = 0.019) and resistin levels (CV 0.58; 95% CI: 0.21, 0.96; p = 0.002), but was not associated with quartile changes in leptin levels. In responders, T-ADP (CV -0.98; 95% CI: -1.88, -0.08; p = 0.031) and resistin (CV -0.95; 95% CI: -1.83, -0.07; p = 0.034) levels decreased 120 minutes after treatment as compared with pretreatment. In addition, in responders, the HMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.041) decreased and the LMW:T-ADP ratio (CV 0.04; 95% CI: 0.01, 0.07; p = 0.043) increased at 120 minutes after treatment. In nonresponders, the LMW:T-ADP ratio (CV -0.04; 95% CI: -0.07, -0.01; p = 0.018) decreased 120 minutes after treatment. Leptin was not associated with treatment response. CONCLUSIONS: Both pretreatment migraine pain severity and treatment response are associated with changes in adipokine levels. Adipokines represent potential novel migraine biomarkers and drug targets.

Ictal adiponectin levels in episodic migraineurs: a randomized pilot trial.

OBJECTIVE: To assess ictal adiponectin (ADP) levels before and after acute abortive treatment in women episodic migraineurs. METHODS: Peripheral blood specimens were collected from women episodic migraineurs before and after acute abortive treatment with sumatriptan/naproxen sodium vs placebo. Univariate and multivariate models were utilized to examine the relationship between serum total ADP (T-ADP), ADP oligomers (high molecular weight [HMW], middle molecular weight, and low molecular weight [LMW]-ADP), and ADP ratio levels and pain severity. Paired t-tests and random intercept longitudinal models were utilized to assess the mean changes in T-ADP, ADP oligomers, and ratios over time in treatment responders and nonresponders. RESULTS: Twenty participants (11 responders, 9 nonresponders) have been studied to date. In all participants, increases in the HMW : LMW ADP ratio were associated with an increase in pain severity. For every 1 point increase in the HMW : LMW ratio, pain severity increased by 0.22 (Confidence Interval [CI]: 0.07, 0.37; P = .004). In contrast, for every 0.25 µg/mL increase in LMW-ADP, pain severity decreased by 0.20 (CI: -0.41, -0.002; P = .047). In treatment responders, T-ADP levels were reduced at 30 minutes (12.52 ± 3.4; P = .03), 60 minutes (12.32 ± 3.2; P = .017), and 120 minutes (12.65 ± 3.2; P = .016) after treatment as compared with onset (13.48 ± 3.8). Additionally, in responders, the HMW : LMW ratio level was greater at pain onset (3.70 ± 1.9 µg/mL) as compared with nonresponders (2.29 ± 0.71 µg/mL), P = .050. Responders also showed a decrease in the HMW : LMW ratio at 60 minutes (2.37 ± 1.1; P = .002) and 120 minutes (2.76 ± 1.4; P = .02) after treatment as compared with onset (3.70 ± 1.9). These changes in responders remained significant after adjusting for covariates, including measured body mass index (m-BMI). Although nonresponders showed no significant changes in unadjusted T-ADP or ADP oligomer or ratio levels, the HMW : LMW ratio was increased in nonresponders after adjustments (P = .025). CONCLUSION: In this pilot study of women episodic migraineurs, the HMW : LMW ADP ratio level was associated with migraine severity and predictive of acute treatment response. ADP and the HMW : LMW ratio of ADP represent potential novel biomarkers and drug targets for episodic migraine.

Should older adults be screened for dementia? It is important to screen for evidence of dementia!

Multiple arguments for considering routine dementia screening have been presented. Furthermore, dementia diagnoses are widely unrecognized. As a result, persons with dementia are missing important clinical care and treatment interventions. By distinction, the problems of defining, diagnosing, and treating mild cognitive impairment (MCI) are not yet resolved, and MCI is not ready for a screening recommendation. Dementia screening approaches, including cognitive testing and functional assessment, must be evaluated on their scientific merits, including sensitivity and specificity for recognizing affected individuals in at-risk populations. Screening tests must be "cost-worthy", with the benefits of true-positive test results justifying the costs of testing and resolving false-positive cases, with due consideration for proper diagnostic evaluation and potential harms. With the tremendous number of new cases projected in the near future and the expected emergence of beneficial therapies, considerably more research is needed to develop more efficient screening systems.

Should older adults be screened for dementia?

The question of whether to screen for dementia and Alzheimer's disease (AD) has been discussed in many forums throughout the world. Generally, medical advisory groups and policy-making groups have recognized the importance of early diagnosis but have uniformly avoided making recommendations to screen at-risk populations. This presentation reflects the support for reconsidering the importance of screening individuals at risk or above a certain age. In this statement, the majority of the authors support the consideration of dementia risk factors in individuals at age 50, with routine yearly screening after 75. Other authors remain concerned that the benefits of treatments of early disease do not yet support a general screening recommendation. These statements are made to encourage progress toward the development of a consensus regarding the widespread institution of screening policy. Accordingly, members of the worldwide scientific community are invited to add their perspective by contributing short commentaries (1500 words) on this subject.