Change In Mini-Mental State Examination Score Research Articles

Self-Reported Hearing Loss, Hearing Aids, and Cognitive Decline in Elderly Adults: A 25-Year Study.

To investigate the association between hearing loss, hearing aid use, and cognitive decline. Prospective population-based study. Data gathered from the Personnes Agées QUID study, a cohort study begun in 1989-90. Individuals aged 65 and older (N = 3,670). At baseline, hearing loss was determined using a questionnaire assessing self-perceived hearing loss; 137 subjects reported major hearing loss, 1,139 reported moderate problems (difficulty following the conversation when several persons talk at the same time or in a noisy background), and 2,394 reported no hearing trouble. Cognitive decline was measured using the Mini-Mental State Examination (MMSE), administered at follow-up visits over 25 years. Self-reported hearing loss was significantly associated with lower baseline MMSE score (β = -0.69, P < .001) and greater decline during the 25-year follow-up period (β = -0.04, P = .01) independent of age, sex, and education. A difference in the rate of change in MMSE score over the 25-year follow-up was observed between participants with hearing loss not using hearing aids and controls (β = -0.06, P < .001). In contrast, subjects with hearing loss using a hearing aid had no difference in cognitive decline (β = 0.07, P = .08) from controls. Self-reported hearing loss is associated with accelerated cognitive decline in older adults; hearing aid use attenuates such decline.

Influence of Amyloid-β on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study.

We hypothesized that comorbid amyloid-beta (Aβ) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack. We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11-labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer's disease. Those with and without Alzheimer's disease-like Aβ deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education. Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group×time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to Aβ deposition. Compared with subjects without Alzheimer's disease-like Aβ deposition, those with Aβ deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Aβ was associated with changes in multiple cognitive domains.

Longitudinal Associations Between Exposure To Ultrafine Particulate Matter And Changes In Cognitive Function Over Five Years Among Puerto Rican Adults Residing In A Major Northeastern U.S. Metropolitan Area

Introduction: Previous studies suggest links between air pollution and cognitive function in adults, but the association between long-term exposure to ultrafine particulate matter (UFP, 60%). Annual residential average UFP exposure (measured as particle number concentration or PNC) was assigned using a model accounting for spatial and temporal trends. We adjusted the PNC values for participants' inhalation rate to obtain the particle inhalation rate (PIR). Multilevel linear models with random intercepts for each participant were used to examine the association between UFP exposure and scores on the Mini-Mental State Examination (MMSE), a validated scale for global cognitive function. We also assessed the association between UFP exposure and change in MMSE score over time. Results: Median PNC was 24000 particles/cc (inter-quartile range (IQR) = 4600 particles/cc). Median PIR was 12.3 billion particles/hr (IQR = 6.1 billion particles/hr). Among individuals without cognitive impairment, PNC was associated with decreased cognitive function (95% CI for an IQR increase in PNC = -0.41, -0.05 points). PIR was also significantly associated with cognitive function levels (95% CI for an IQR increase in PIR = 0.022, 0.28 points). Interactions were evident by sex, employment status, depression, cardiovascular disease, and diabetes. Restricting the analysis to participants with more than an 8th grade education did not change the results. Discussion: UFP was associated with global cognitive function and the rate of cognitive decline over five years.

Effects of low blood pressure in cognitively impaired elderly patients treated with antihypertensive drugs.

The prognostic role of high blood pressure and the aggressiveness of blood pressure lowering in dementia are not well characterized. To assess whether office blood pressure, ambulatory blood pressure monitoring, or the use of antihypertensive drugs (AHDs) predict the progression of cognitive decline in patients with overt dementia and mild cognitive impairment (MCI). Cohort study between June 1, 2009, and December 31, 2012, with a median 9-month follow-up of patients with dementia and MCI in 2 outpatient memory clinics. Cognitive decline, defined as a Mini-Mental State Examination (MMSE) score change between baseline and follow-up. We analyzed 172 patients, with a mean (SD) age of 79 (5) years and a mean (SD) MMSE score of 22.1 (4.4). Among them, 68.0% had dementia, 32.0% had MCI, and 69.8% were being treated with AHDs. Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤ 128 mm Hg) showed a greater MMSE score change (mean [SD], -2.8 [3.8]) compared with patients in the intermediate tertile (129-144 mm Hg) (mean [SD], -0.7 [2.5]; P = .002) and patients in the highest tertile (≥ 145 mm Hg) (mean [SD], -0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs. In a multivariable model that included age, baseline MMSE score, and vascular comorbidity score, the interaction term between low daytime SBP tertile and AHD treatment was independently associated with a greater cognitive decline in both subgroups. The association between office SBP and MMSE score change was weaker. Other ambulatory blood pressure monitoring variables were not associated with MMSE score change. Low daytime SBP was independently associated with a greater progression of cognitive decline in older patients with dementia and MCI among those treated with AHDs. Excessive SBP lowering may be harmful for older patients with cognitive impairment. Ambulatory blood pressure monitoring can be useful to help avoid high blood pressure overtreatment in this population.

The association between the severity of poststroke depression and clinical outcomes after first-onset stroke in Korean patients

ObjectiveThe purpose of the present study is to evaluate the association between poststroke depression (PSD) and clinical outcomes in first-onset stroke patients who are undergoing a rehabilitation program. MethodsThe present study included 180 inpatients that were recruited consecutively and followed up over a 6-month observational period. Poststroke depression was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Symptoms of depression and clinical outcomes were assessed using the Beck Depression Inventory, the modified Barthel Index (MBI) and the Mini Mental State Examination (MMSE). All patients were assessed at baseline and at the end of the 6-month observational period. ResultsOf the 180 patients, 127 (70.6%) were diagnosed with minimal-to-mild depression (MMD), and 53 (29.4%) were diagnosed with moderate-to-severe depression (MSD). The mean change in MBI scores from baseline to 6 months was significantly higher (P=.029) in the MMD group (23.8) than in the MSD group (8.6). The odds ratio for an unfavorable outcome (MBI score <60) in patients with MSD was approximately 3.5 in relation to patients with MMD. The mean change in MMSE score (4.4 versus 7.4) was not significantly different between the MMD and MSD groups. ConclusionThe present findings suggest that the severity of PSD may be associated with clinical outcomes in Korean patients 6 months after a first-onset stroke. Our data agree with previous findings, which indicate that clinicians should carefully evaluate symptoms of depression in stroke patients during routine clinical practice. The methodological shortcomings of the present study may require further studies with adequate power and improved design to clarify the association between PSD and clinical outcomes following stroke.

Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study—a randomized controlled trial

Background: Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities.Objective: The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects.Design: This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT).Results: The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (−8.6 ± 0.4 and −16.5 ± 0.8 s, respectively) and IF (−6.7 ± 0.5 and −14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (−0.8 ± 1.6 and −1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r2 = 0.1703, P < 0.0001).Conclusions: This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. This trial was registered at www.controlled-trials.com as ISRCTN68970511.

Pharmacogenetics of cerebrovascular metabolism modulators in dementia due to Alzheimer’s disease

The aims of this study were to investigate risk factors for cognitive and functional decline among 193 patients with Alzheimer’s disease dementia (AD), and to conduct pharmacogenetic analysis on cerebrovascular metabolism modulators, taking into account APOE haplotypes and the genotypes of ACE, CETP, LDLR and the LXR-β gene. For all patients, later age at AD onset was the most important risk factor for faster cognitive and functional decline, while the late-life coronary heart disease risk was inversely related to cognitive decline only for carriers of APOE4+ haplotypes. Schooling was protective against cognitive decline only for women and carriers of APOE4+ haplotypes, while higher body mass index in late life was protective against cognitive decline only for men. Carriers of the APOE-e4/e4 haplotype had earlier AD onset, whereas genotypes of CETP and LDLR that had traditionally been associated with higher risk of AD were associated with later onset of dementia. Angiotensin-converting enzyme inhibitors caused a 50% reduction in Mini-Mental State Examination score changes, and had better disease-modifying properties than did centrally-acting angiotensin-converting enzyme inhibitors alone. Angiotensin receptor blockers had genetically mediated effects that led to faster cognitive and functional decline, while patients with genetic tendencies towards faster cognitive and functional decline had maximum benefits when they used lipophilic statins, and vice versa.

Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled, confirmatory phase III trial.

IntroductionThe efficacy of a cholinesterase inhibitor, donepezil, in patients with dementia with Lewy bodies (DLB) was investigated to confirm the superiority over placebo in the 12-week, double-blind phase of this phase III study.MethodsPatients with probable DLB (n = 142) were randomly assigned to placebo or to 5 mg or 10 mg of donepezil administered once daily for 12 weeks. The co–primary endpoints were changes in cognitive function assessed using the Mini-Mental State Examination (MMSE) and behavioral and neuropsychiatric symptoms using the Neuropsychiatric Inventory (NPI-2: hallucinations and fluctuations). The superiority of each active group over placebo was determined with simultaneous statistical significance in both endpoints. Safety evaluations included adverse events (AEs) and the unified Parkinson's disease rating scale (UPDRS) part III.ResultsThe predefined superiority of donepezil to the placebo was not confirmed in either active group in the primary analysis. MMSE score significantly improved compared to placebo in the 10 mg group (10 mg: 2.2 ± 0.4, placebo: 0.6 ± 0.5 (mean ± standard error); P = 0.016). The change in MMSE score in the 5 mg group was not significant (1.4 ± 0.5 (mean ± standard error); P = 0.232). Although NPI-2 improved compared to baseline in the active groups, the differences from placebo were not significant. Most AEs were mild or moderate. Although the incidence of parkinsonism was slightly higher in the 10 mg group, the change in the UPDRS score was minimal and without a significant difference from the placebo group.ConclusionsThe co–primary endpoints were not achieved in this trial. However, significant improvement in MMSE score was demonstrated with 10 mg, but not 5 mg, of donepezil. The evaluation of psychiatric symptoms might be affected by advanced education and instructions given to caregivers. Overall, donepezil was well tolerated in patients with DLB. With careful attention on gastrointestinal or parkinsonian symptoms, patients with DLB can safely benefit from treatment with donepezil.Trial registrationClinicalTrials.gov Identifier: NCT01278407 (trial registration date: 14 January 2011)Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-014-0083-0) contains supplementary material, which is available to authorized users.

ALZHEIMER’S COGNITIVE IMPAIRMENT CAN BE CURED BY DECREASING BLOOD HOMOCYSTEIC ACID

Recent big two clinical trials of amyloid beta treatment for Alzheimer’s disease are all failed to recover the cognitive impairment, it has forced us to reconsider the central hypothesis of amyloid pathogen for Alzheimer’s disease. We recently published that human Alzheimer’s patients showed the strong relationship between Mini Mental State Examination (MMSE) scores and blood homocysteic acid (HA) level. However this relationship did not show the pathogenic action of HA. So we investigated the pathogenic effect of blood HA on MMSE score, that is, how does blood HA level change affect MMSE score? 6 AD patients (all female: age 77, 82, 86,87, 91, 91) were given green tea powder 1g at every meal for 2 months. Their blood HA level and MMSE score were measured before and after taking green tea powder. The relationship between blood HA level change and MMSE score change was investigated. The strong statistically significant negative relationship between blood HA level change and MMSE score change: r=-0.96, p=0.00018, n=6. From our observation, it shows that blood HA level change induced MMSE score change, that is, Alzheimer’s cognitive ability was controlled by blood HA level. Now we can present that some healthy food, that is named HBF, can recovered 100% Alzheimer’s cognitive impairment by the decreasing the homocysteic acid in a peripheral blood. We made the open-trial of HBF on the Alzheimer’s and lewy bodies dementia’s cognitive recovery. Two male lewy bodies dementia patients, 11 female Alzheimer’s patients were enrolled. All patients were at end stage. They ingested HBF supplement 1.5g at every meals for 1-2 months. Their MMSE scores were measured before and after their HBF ingestion. Their blood homocysteic acid levels were measured by ELISA method before and after their ingestions. Results were extremely amaging. 100% of all patients showed their cognitive recovery. Their blood homocysteic acid decreased their level by HBF. Now we have made a relative large open trial of AD patients. 91 patients were enrolled. Their cognitive recovery were measured by NM scale (New Clinical Scale for Rating of Mental States). All patients who took HBF showed the recovery of their behaviors. From this open-trial of HBF, many facts can be confirmed. (1) Alzheimer’s cognitive impairment can be recovered at even end stage. (2) Alzheimer’s disease is induced by homocysteic acid.

Cognitive Function After Carotid Endarterectomy: Early Decline and Later Recovery.

To prospectively study neurocognitive performance following carotid endarterectomy (CEA) in various follow-up periods, taking into account the potential confounding factors. Thirty-six patients with carotid artery stenosis received CEA (group A). Thirty-one patients underwent surgery for femoropopliteal occlusive disease served as controls (group B). Neuropsychological testing and brain magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) was repeated preoperatively, within 3 days and at 3 months after surgery. No patient had DWI evidence of procedure-related cerebral ischemia. Preoperative baseline scores of groups A and B were not statistically different in mini mental state examination (MMSE) or clock drawing task (CDT) score. MMSE and CDT scores were significantly reduced for patients in group A (p < 0.01) within 3 days after CEA. Differences of MMSE score (p=0.48) and CDT score (p=0.26) between baseline and 3 months after surgery in group A were not statistically significant. No statistically significant change of MMSE score and CDT score in group B was observed at 3 days and 3 months after the surgery. Degree of internal carotid artery (ICA) stenosis (p=0.029) and duration of ICA clamping (p=0.031) were significantly higher in patients with cognitive impairment immediately after CEA than in those without that. Our study demonstrated cognitive decline for the patients with unilateral carotid stenosis at early stage after CEA and a restorative effect at 3 months after CEA. Postoperative early cognitive impairment might be associated with intraoperative temporary hypoperfusion and postoperative hyperperfusion, not the microembolic event.

The cross-sectional and longitudinal associations of diabetic retinopathy with cognitive function and brain MRI findings: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

OBJECTIVELongitudinal evidence linking diabetic retinopathy with changes in brain structure and cognition is sparse. We used data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to determine whether diabetic retinopathy at baseline predicted changes in brain structure or cognition 40 months later.RESEARCH DESIGN AND METHODSParticipants from the ACCORD-MIND and ACCORD-Eye substudies were included in analyses of cognition (n = 1,862) and MRI-derived brain variables (n = 432). Retinopathy was categorized as none, mild nonproliferative, or moderate/severe. Tests of cognition included the Mini-Mental State Examination (MMSE), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test, and Stroop test. Primary brain outcomes were gray matter and abnormal white matter volumes.RESULTSBaseline retinopathy was associated with lower gray matter volume (adjusted means of 470, 466, and 461 cm3 for none, mild, and moderate/severe retinopathy, respectively; P = 0.03). Baseline retinopathy also predicted a greater change in MMSE and DSST scores at 40 months in each retinopathy category (MMSE: −0.20, −0.57, and −0.42, respectively [P = 0.04]; DSST: −1.30, −1.84, and −2.89, respectively[P = 0.01]).CONCLUSIONSDiabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes. Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline, patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline.

Sleep duration and memory in the elderly Chinese: longitudinal analysis of the Guangzhou Biobank Cohort Study.

Previous cross-sectional studies showed that short or long sleep duration was associated with memory impairment (MI), but longitudinal studies are scarce. We examined whether sleep duration was associated with memory decline or development of MI. We conducted a prospective analysis based on the Guangzhou Biobank Cohort Study on 13,888 participants aged 50+ years without MI at baseline and with a follow-up for a mean of 4.1 years. Memory decline was assessed using the Delayed 10-Word Recall Test (DWRT), and in a subset (n = 6,020) with the Mini-Mental State Examination (MMSE). Short and long sleep duration was defined as ≤ 5 hours/day and ≥ 9 hours/day, respectively. Data were analyzed both continuously for memory decline and dichotomously for MI (independently defined as DWRT, < 4; MMSE, < 25). After adjusting for multiple potential confounders, both short and long sleep durations were associated with memory decline using DWRT or MMSE score changes (all P < 0.001). Seven percent (n = 980) developed DWRT-defined MI and 4.0% (n = 194) MMSE-defined MI during the follow-up. Only those with a short (≤ 5 h/day) sleep duration had a significantly increased risk of DWRT-defined MI (odds ratio = 1.53 (95% confidence interval; 1.21-1.93); P < 0.001) relative to normal sleepers (7 h/day). The association remained significant after excluding those with poor self-reported health. No associations were observed with MMSE-defined MI for both long and short sleep durations. This is the largest study to date addressing the association between extremes of sleep duration and memory decline. The observed adverse relationships provide support for an intervention study to examine the potential benefits of normalizing sleep duration in attenuating memory decline.

Vascular Risk as a Predictor of Cognitive Decline in a Cohort of Elderly Patients with Mild to Moderate Dementia

Background/Aims: The purpose of our study was to evaluate vascular risk factors and other clinical variables as predictors of cognitive and functional decline in elderly patients with mild to moderate dementia. Methods: The clinical characteristics of 82 elderly patients (mean age 79.0 ± 5.9 years; 67.1% females) with mild to moderate dementia were obtained at baseline, including years of education, Framingham Coronary Heart Disease Risk score, Hachinski Ischemic Score (HIS), Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) score, Functional Activities Questionnaire (FAQ) score, Burden Interview Scale score, and Neuropsychiatric Inventory (NPI) score. Changes in MMSE and FAQ scores over time were assessed annually. The association between baseline clinical variables and cognitive and functional decline was investigated during 3 years of follow-up through the use of generalized linear mixed effects models. Results: A trend was found towards steeper cognitive decline in patients with less vascular burden according to the HIS (β = 0.056, p = 0.09), better cognitive performance according to the CDR score (β = 0.313, p = 0.06) and worse caregiver burden according to the Burden Interview Scale score (β = -0.012, p = 0.07) at baseline. Conclusion: Further studies with larger samples are necessary to confirm and expand our findings.

Cognitive stimulation in cognitively impaired individuals and cognitively healthy individuals with a family history of dementia: short-term results from the "Allena-Mente" randomized controlled trial.

We evaluated the short-term efficacy of a protocol of cognitive stimulation (CS), compared with a sham intervention, on cognitive performance in cognitively healthy individuals with a family history of dementia (NDFAM) and in non-demented individuals with cognitive impairment (CI). We performed a randomized controlled trial of CS in NDFAM and CI. CS consisted in 10 twice weekly meetings of CS focused on a specific cognitive area. CS was compared with a sham intervention (CT) using Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Corsi test. All study participants were typed for the presence of apolipoprotein E (APOE)-Ɛ4. Cognitively healthy NDFAM showed a higher net cognitive gain after CS, as reflected in their MoCA score, and a borderline significant net increase in visuospatial memory (Corsi test) compared with those receiving the CT. APOE-Ɛ4 carriers showed a less significant improvement on the Corsi test with respect to APOE-Ɛ4 non-carriers. In the CI sample, the MoCA and Corsi test results did not differ between the cognitively stimulated subjects and the controls. No changes in MMSE scores were found in either sample of subjects. These findings suggest that CS as structured in this study is an effective treatment in cognitively healthy individuals, whereas it is less effective in individuals with CI. Moreover, evaluation of APOE-Ɛ4 status provided evidence of a substantial genetic contribution to the efficacy of CS on visuospatial memory as measured using the Corsi test.

Cognitive deterioration in bilateral asymptomatic severe carotid stenosis.

This study aimed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile, and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler-based breath-holding index test. As a measure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bilaterally abnormal breath-holding index (P<0.0001). Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change. Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments.

Effect of cerumen impaction on hearing and cognitive functions in Japanese older adults with cognitive impairment

To assess the effect of cerumen impaction and its removal on hearing ability and cognitive function in elderly patients with memory disorders in Japan. Pure tone audiometry (PTA) and the Mini-Mental State Examination (MMSE) were administered to participants before and after cerumen removal. Participants who had cerumen impaction in the better-hearing ear comprised the case group; the control group consisted of participants who either did not have cerumen impaction or had it in the worse hearing ear. Hearing and cognition changes were compared between the groups after cerumen removal. A total of 55 patients who completed all examinations were assigned to the case group (29 patients) or the control group (26 patients). The average hearing change was 4.6 ± 7.4 in the case group and 0.9 ± 0.9 in the control group (P = 0.029). The average change in MMSE score was 0.7 ± 2.5 in the case group and -1.0 ± 4.1 in the control group (P = 0.068). The case group showed a significant improvement in MMSE scores after age adjustment compared with the control group (P = 0.049). Hearing improved significantly in the case group relative to controls after cerumen removal. A significant cognitive improvement in the case group relative to controls was additionally observed after cerumen removal with age adjustment. Thus, the present results suggest routine ear canal examinations might benefit elderly individuals with memory disorders.

Cilostazol Add-On Therapy in Patients with Mild Dementia Receiving Donepezil: A Retrospective Study

GoalCombinatorial therapy directed at both vascular and neurodegenerative aspects of dementia may offer a promising strategy for treatment of dementia, which often has a multifactorial basis in the elderly. We investigated whether the phosphodiesterase III inhibitor cilostazol, which is often used in the prevention of stroke and peripheral artery disease, may delay cognitive decline in the elderly receiving donepezil.MethodsMedical records were retrospectively surveyed to identify patients who had received donepezil for more than one year and had undergone Mini-Mental State Examination (MMSE) at least at two time points. Those with an initial MMSE score of less than 27 points were subjected to analysis (n = 156), with a cut-point of 21/22 applied to assign them to mild (n = 70) and moderate/severe (n = 86) dementia. The change of total MMSE score per year was compared between patients who had received donepezil and those given both donepezil and cilostazol.FindingsIn patients with mild dementia who had received donepezil and cilostazol (n = 34; 77.2±6.8 years old), the annual change in MMSE score was −0.5±1.6 during an observational period of 28.6±11.7 months, with those receiving donepezil only (n = 36; 78.4±6.5 years old) scoring less (−2.2±4.1) during 30.4±12.8 months with a statistical intergroup difference (p = 0.022). Multivariate analysis showed that absence of cilostazol treatment was the only significant predictor of MMSE decline. A positive effect of cilostazol was found in three subscale scores of MMSE, orientation for time or place and delayed recall. By clear contrast, in patients with moderate/severe dementia, there were no intergroup differences in decrease of total or subscale MMSE scores between the two groups.ConclusionsThese results suggest potential for cilostazol treatment in the suppression of cognitive decline in patients receiving donepezil with mild dementia but not in those with moderate/severe dementia.

Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer&amp;#39;s disease

BackgroundCurrently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD.MethodsIn this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model.ResultsIn all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18.27]) versus the galantamine group (−8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group.ConclusionLong-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients.IdentificationThis study is registered at ClinicalTrials.gov (NCT00679627).

Decrease in daytime sleeping is associated with improvement in cognition after hospital discharge in older adults.

To examine the relationship between changes in objectively assessed sleep and global cognitive functioning from inpatient postacute rehabilitation to 6-month follow-up. Secondary analysis of two prospective, longitudinal studies. Inpatient rehabilitation units at a Veterans Affairs Medical Center. Older adults (mean age 73.8 ± 9.4) undergoing inpatient rehabilitation (n = 192). All participants completed 7 nights and days of ambulatory sleep monitoring using wrist actigraphy (yielding an estimate of nighttime wakefulness and daytime sleep) and the Mini-Mental State Examination (MMSE) during a postacute inpatient rehabilitation stay and 6 months after discharge. The 5-item Geriatric Depression Scale, Geriatric Pain Measure, and Cumulative Illness Rating Scale for Geriatrics were completed during inpatient rehabilitation. Growth curve modeling (controlling for baseline age, education, sex, body mass index, depression, pain, and comorbidity burden) revealed that individuals whose amount of daytime sleep decreased from inpatient postacute rehabilitation to 6-month follow-up also experienced improvements in MMSE score (β = -0.01, t(80 = -3.22, P = .002)). Change in nighttime wakefulness was not a significant predictor of change in MMSE score. Older adults whose daytime sleeping decreased after hospital discharge also experienced improvements in cognitive functioning at 6 month follow-up. As such, daytime sleep may represent a promising candidate for targeted interventions aimed at promoting cognitive recovery after hospital discharge.

Cilostazol improves cognitive function in patients with mild cognitive impairment: a retrospective analysis.

Cerebral ischemia and accumulation of amyloid β (Aβ) are major risk factors for the development of dementia, including vascular dementia and Alzheimer's disease. Cilostazol, an antiplatelet drug, has been shown to improve cerebral circulation and reduce accumulation of Aβ. In this study, the long-term effect of cilostazol on cognitive function was investigated retrospectively. Medical records at Sumotoitsuki Hospital were surveyed to find all patients treated with cilostazol and evaluated by the Mini-Mental State Examination (MMSE) during at least two visits separated by an interval of more than 6 months. Patients receiving anti-dementia drugs were excluded. Temporal changes in MMSE scores were compared between patients treated with cilostazol (n = 70) and those who ceased administration of this drug (n = 22). The mean follow-up period was 691 days. Decrease in MMSE score was significantly ameliorated by administration of cilostazol. Subgroup analysis revealed that cilostazol significantly improved MMSE score in patients with mild cognitive impairment, though no significant effect was observed in patients with normal cognitive function or dementia. Although there are limitations to such a retrospective study, these results significantly encourage undertaking a prospective cohort study to determine the effect of cilostazol on mild cognitive impairment where no treatments currently exist.