The stability of AQT processing speed,ADAS‐Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer’s disease

Wiig EH, Annas P, Basun H, Andreasen N, Lannfelt L, Zetterberg H, Blennow K, Minthon L. The stability of AQT processing speed, ADAS‐Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 186–193.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer’s disease (AD). Materials and methods – Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog), and MMSE were administered concurrently. Results – Correlations (ρ) between age and AQT processing speed were non‐significant, but were significant for ADAS‐Cog and Mini Mental State Examination (MMSE). AQT and ADAS‐Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman’s ρ) were moderate‐to‐high for all tests. Means for subgroups did not differ as a function of medication type. Conclusions – AQT processing speed, ADAS‐Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.     

Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease

Mateo I, Infante J, Sánchez‐Juan P, García‐Gorostiaga I, Rodríguez‐Rodríguez E, Vázquez‐Higuera JL, Berciano J, Combarros O. Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 136–138.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase‐1 (HO‐1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up‐regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO‐1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO‐1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO‐1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO‐1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO‐1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO‐1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.     

Sunlight exposure is important for preventing hip fractures in patients with Alzheimer's disease, Parkinson's disease, or stroke

Iwamoto J, Takeda T, Matsumoto H. Sunlight exposure is important for preventing hip fractures in patients with Alzheimer’s disease, Parkinson’s disease, or stroke.
Acta Neurol Scand: 2012: 125: 279–284.
© 2011 John Wiley & Sons A/S. Objectives – Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. Methods – The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer’s disease, Parkinson’s disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta‐analysis) was performed. Results – Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer’s disease, 0.27 (0.08, 0.96) for Parkinson’s disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. Conclusion – The present meta‐analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer’s disease, Parkinson’s disease, and stroke.     

Two galantamine titration regimens in patients switched from donepezil

Engedal K, Davis B, Richarz U, Han J, Schäuble B, Andreasen N. Two galantamine titration regimens in patients switched from donepezil.
Acta Neurol Scand: 2012: 126: 37–44.
© 2011 John Wiley & Sons A/S. Objectives – In addition to inhibiting acetylcholinesterase, galantamine has allosteric‐modulating activity at nicotinic receptors. This may make galantamine an attractive option for patients starting treatment for Alzheimer’s disease (AD), but also for those who have not benefited from their current therapy. This study explored outcomes in subjects with AD transitioning from donepezil because of insufficient tolerability or efficacy. Materials and methods – Subjects previously receiving donepezil for mild‐to‐moderate AD were enrolled in a 12‐week randomized, open‐label study. After screening and a 7‐day washout, subjects were randomly allocated to galantamine fast (8 mg/week increments) or slow (8 mg/4 week) titration to 16–24 mg. Efficacy outcomes included the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS‐cog/11), Mini‐Mental State Examination (MMSE), Clinician’s Interview‐Based Impression of Change – Plus Caregiver’s Input (CIBIC‐plus) and Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory (ADCS‐ADL). Results – Eighty‐six of 89 patients (fast titration, n = 44; slow titration, n = 45) completed the study. At week 12, ADAS‐cog/11 score improved from screening by 2.6 and 0.6 in the fast‐ and slow‐titration arms, respectively (overall, ?1.6; P = 0.002). MMSE scores improved slightly in both arms (overall, +0.9; P = 0.002). Two‐thirds of patients had improvement or no change on the CIBIC‐plus at week 12. ADCS‐ADL scores did not change significantly from screening in either treatment arm. Galantamine was generally well tolerated; nausea (5.6%) and bradycardia (4.5%) were the most commonly reported adverse events. Conclusions – Patients in whom donepezil is ineffective or poorly tolerated may benefit from a switch to galantamine.     

Long-term rivastigmine treatment in a routine clinical setting

Objective – The aim of the study was to observe the effects of long‐term rivastigmine treatment in patients with mild to moderate Alzheimer’s disease (AD) in a routine clinical setting. Methods – This was a prospective, open‐label, observational, multicentre, non‐randomized study. Outcome measures included the Mini Mental State Examination (MMSE), the Clinician’s Interview‐Based Impression of Change (CIBIC) and the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS‐cog). Results – Of 217 patients initiated into rivastigmine treatment, 62% (n = 135) remained on treatment for 24 months. Most patients droped out due to nursing home placement or side effects. Eighty per cent and 67% of completers exhibited a symptomatic attenuation of cognitive decline (≤ 4‐point deterioration) as assessed by using the MMSE and ADAS‐cog respectively. Forty‐four per cent showed an unchanged/improved CIBIC rating. Conclusions – Over 60% of patients remained on treatment for 2 years in this routine clinical setting. In patients who remained on treatment, rivastigmine appeared to stabilize their condition and prevented or delayed symptomatic decline.     

Tetranectin and apolipoprotein A‐I in cerebrospinal fluid as potential biomarkers for Parkinson’s disease

Wang E‐S, Sun Y, Guo J‐G, Gao X, Hu J‐W, Zhou L, Hu J, Jiang C‐C. Tetranectin and apolipoprotein A‐I in cerebrospinal fluid as potential biomarkers for Parkinson’s disease.
Acta Neurol Scand: 2010: 122: 350–359.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – The application of biomarkers may potentially improve the efficiency of the diagnosis for Parkinson’s disease (PD). However, no reliable biomarker has been identified to date. This study is aimed to identify proteins that might serve as potential biomarkers for PD diagnosis or pathogenesis. Materials and methods – Two‐dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF MS), was used to determine the differentially expressed cerebrospinal fluid (CSF) proteins in PD patients (n = 3) compared with normal controls (n = 3). Selected proteins were further confirmed by Western blotting analysis in the CSF of PD patients (n = 8), Alzheimer’s disease (AD) patients (n = 6) and normal control subjects (n = 7). Results – Eight proteins were identified after MS and protein database interrogation. In the CSF of PD patients, the expression levels of one isoform of apolipoprotein A‐I (apoA‐I), tetranectin, myosin phosphatase target subunit 1 (MYPT1), and two unknown proteins were down‐regulated, whereas the expression levels of another apoA‐I isoform, proapolipoprotein, and lipoprotein were up‐regulated. Western blotting indicates that the expression of tetranectin was reduced in the CSF from PD patients and elevated in AD, while the expression of apoA‐I was changed only in the CSF from PD patients. Conclusion – Our preliminary results suggest that tetranectin and apoA‐I may serve as potential biomarkers for PD, though further validation is needed.     

Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson’s disease

Ishibashi K, Kanemaru K, Saito Y, Murayama S, Oda K, Ishiwata K, Mizusawa H, Ishii K. Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson’s disease.
Acta Neurol Scand: 2010: 122: 46–51.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To evaluate the association between cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations and nigrostriatal dopaminergic function assessed by positron emission tomography (PET) imaging with carbon‐11‐labeled 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐tropane (¹¹C‐CFT), which can measure the dopamine transporter (DAT) density, in Parkinson’s disease (PD). Methods – ¹¹C‐CFT PET scans and CSF examinations were performed on 21 patients with PD, and six patients with non‐parkinsonian syndromes (NPS) as a control group. Results – In the PD group, CSF HVA concentrations were significantly correlated with the striatal uptake of ¹¹C‐CFT (r = 0.76, P < 0.01). However, in the NPS group, two indices were within the normal range. Conclusions – In PD, CSF HVA concentrations correlate with nigrostriatal dopaminergic function. Therefore, CSF HVA concentrations may be an additional surrogate marker for estimating the remaining nigrostriatal dopaminergic function in case that DAT imaging is unavailable.     

Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer’s disease

Background and purpose: Life style‐related disorders such as hypertension, diabetes, dyslipidemia, and obesity are reported to be a great risk of dementia. Adipocytokines released from adipose tissue are thought to modulate some brain functions including memory and cognition. We here analysed adiponectin, one of the most important adipocytokines, in plasma and cerebrospinal fluid (CSF) from cognitive normal controls (NC), mild cognitive impairment (MCI) subjects, and patients with Alzheimer’s disease (AD) and discussed if/how adiponectin could relate to the pathogenesis of AD. Methods: Normal controls (n = 28), MCI (n = 18), and AD (n = 27) subjects were recruited at Tohoku University Hospital. The diagnosis of AD was based on NINCDS‐ADRDA criteria. All the blood and CSF samples were obtained from each fasted subject. Adiponectin was assayed using a sandwich ELISA system. Results: The levels of adiponectin between in plasma and in CSF showed a positive correlation. Plasma adiponectin was significantly higher in MCI and AD compared to NC, whereas CSF adiponectin was significantly higher in MCI compared to NC. Conclusion: It is possible that the level of adiponectin in plasma reflects its level in CSF. The tendency to have higher adiponectin in plasma and CSF from MCI and AD suggests that this molecule plays a critical role in the onset of AD.     

Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized,double‐blind,controlled trial investigating three dosages of Cerebrolysin

Background: Cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer’s disease (AD) (ITT data set: N = 133; MMSE: 14–20) included in a dose‐finding study (ITT data set: N = 251; MMSE: 14–25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21–25) are also presented. Methods: Patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS‐cog+ (Alzheimer’s Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview‐based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. Results: At week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10‐, 30‐ and 60‐ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail‐making test) were not significant. Cerebrolysin was safe and well tolerated. Conclusions: These results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose‐specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.     

Inclusion body myositis in Alzheimer's disease

Roos PM, Vesterberg O, Nordberg M. Inclusion body myositis in Alzheimer’s disease.
Acta Neurol Scand: 2011: 124: 215–217.
© 2010 John Wiley & Sons A/S. Background – The prevalence of Alzheimer’s disease is increasing. Could findings of similar deposits in brain and muscle tissue explain this increase? The purpose of this report is to illustrate that Alzheimer’s disease and inclusion body myositis may share a common aetiology. Results – We present a case where Alzheimer’s disease and inclusion body myositis coexist in the same patient. Amyloid‐beta deposition and the presence of phosphorylated tau protein have been noted in brain tissue and in muscle biopsy from patients with these disorders. Methods – Electrophysiological methods are needed for proper diagnosis of this brain and muscle disorder. Recent data on deposit structures in both conditions may indicate an environmental aetiology for Alzheimer’s disease and inclusion body myositis. Conclusion – By combining electrophysiological methods with muscle biopsy in cases of Alzheimer’s disease, the possible aetiological connection between simultaneous affection of both muscle and brain in this condition can be established.     

Alzheimer CSF biomarkers in routine clinical setting

Tabaraud F, Leman JP, Milor AM, Roussie JM, Barrière G, Tartary M, Boutros‐Toni F, Rigaud M. Alzheimer CSF biomarkers in routine clinical setting.
Acta Neurol Scand: 2012: 125: 416–423.
© 2011 John Wiley & Sons A/S. Objectives – Our work was aimed to evaluate Alzheimer’s disease diagnosis improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily practice. Materials and Methods – For this purpose, 150 patients clinically and neurochemically classified as having AD or cognitive impairment with or without other dementia type were included in the study. The following CSF peptides were studied, blindly to the clinical diagnosis: beta‐amyloid_1–42 peptide (Aβ_1–42), Tau (T‐tau), threonine‐181 hyperphosphorylated tau protein (P‐tau₁₈₁), and beta‐amyloid_1–40 peptide (Aβ_1–40). From these measurements, Innotest® Amyloid Tau Index (IATI) was calculated for each patient. Results – This assessment allowed to separate 83 biochemical profiles of AD and 67 non‐Alzheimer’s disease (non‐AD), both AD and non‐AD categories match with clinical data amounting to 73% and 90%, respectively. Among mild cognitive impairment (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD. We devoted a special section to Aβ_1–40 which is not a routine parameter but can help to confirm a pathological amyloid process as Aβ_1–42/Aβ_1–40 ratio underlining the real decline of the Aβ_1–42. Conclusions – The interest of biomarkers and their ability to solve awkward cases were carefully noticed all the more when a discrepancy between clinical and CSF biological data was involved. The final proposed algorithm allowed to identify pathogenic forms of AD according to the prevailing role of hyperphosphorylated tau or amyloid beta peptide.     

Leptin and ghrelin concentrations and weight loss in Parkinson’s disease

Fiszer U, Micha?owska M, Baranowska B, Wolińska‐Witort E, Jeske W, Jethon M, Pia?cik‐Gromada M, Marcinowska‐Suchowierska E. Leptin and ghrelin concentrations and weight loss in Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 230–236.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To investigate the role of leptin, ghrelin, GH and IGF‐1 in energy balance disturbances in Parkinson’s disease (PD). Materials and methods – Thirty‐nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF‐1, TSH, T3 and T4, concentrations were evaluated. Results – A lower plasma leptin concentration and a higher serum IGF‐1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss. Conclusion – These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.     

Non-interventional surveillance study of adverse events in patients with epilepsy

Cruise KE, Bucks RS, Loftus AM, Newton RU, Pegoraro R, Thomas MG. Exercise and Parkinson’s: benefits for cognition and quality of life.
Acta Neurol Scand: 2011: 123: 13–19.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson’s disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease‐specific QoL for people with PD. Methods – Twenty‐eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Results – Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease‐specific QoL. Conclusions – These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD.     

Serum somatostatin in early‐stage Parkinson’s disease

Shiraishi M, Kobayashi T, Watanabe H, Kamo T, Hasegawa Y. Serum somatostatin in early‐stage Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 225–229.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To compare levels of plasma digestive hormones in patients with and without nausea or vomiting during initial treatment of early‐stage Parkinson’s disease (PD). Methods – This was a 3‐week, open‐label, randomized study of treatment with an antiparkinson drug in untreated PD patients. We measured the levels of plasma digestive hormones before (baseline) and 3 weeks after administration of an antiparkinson drug. Results – Mean value of serum somatostatin at baseline was significantly increased in PD patients compared with the control group (P < 0.01). Serum somatostatin levels were significantly increased after treatment in subjects who experienced nausea or vomiting (P < 0.01). However, significant increase in serum somatostatin levels after treatment was not observed in PD patients without nausea or vomitting. Conclusion – Serum somatostatin in early‐stage PD patients before treatment was increased compared with healthy subjects. The nausea and vomiting induced by antiparkinson drugs may be related to uncontrolled somatostatin secretion through central vagus nerve dysfunction .     

The comparative efficacy and safety of cholinesterase inhibitors in patients with mild‐to‐moderate Alzheimer's disease: a Bayesian network meta‐analysis

Background

Comparative evidence for efficacy and safety of second‐generation cholinesterase inhibitors (ChEIs) is still sparse.

Objectives

The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild‐to‐moderate Alzheimer's disease (AD).

Methods

We conducted a systematic review for published articles and included randomised, double‐blind, placebo‐controlled trials and head‐to‐head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS‐Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview‐Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta‐analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions.

Results

Among the 21 trials included, network meta‐analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS‐Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety.

Conclusions

Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild‐to‐moderate AD.     

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease

Constantinescu R, Holmberg B, Rosengren L, Corneliusson O, Johnels B, Zetterberg H. Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 206–210.
© 2010 John Wiley & Sons A/S. Objectives – Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non‐specific marker of neuronal damage, are normal in Parkinson’s disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF‐NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. Materials and methods – CSF‐NFL levels were measured consecutively in eight patients with PD before and after STN‐DBS treatment. Results – CSF‐NFL levels were normal prior to STN‐DBS and increased sharply during the first 2 weeks post‐operatively, but normalized after 12 months or more. Conclusion – The STN‐DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF‐NFL levels at 12 months post‐operatively and beyond suggest the absence of any long‐term neuronal damage caused by long‐term STN‐DBS stimulation.     

Prevalence and European comparison of dementia in a ≥75‐year‐old composite population in Spain

Virués‐Ortega J, de Pedro‐Cuesta J, Vega S, Seijo‐Martínez M, Saz P, Rodríguez F, Rodríguez‐Laso Á, Reñé R, de las Heras SP, Mateos R, Martínez‐Martín P, Mahillo‐Fernández I, López‐Pousa S, Lobo A, Reglà JL, Gascón J, García FJ, Fernández‐Martínez M, Boix R, Bermejo‐Pareja F, Bergareche A, Sánchez‐Sánchez F, de Arce A, del Barrio JL; On behalf of the Spanish Epidemiological Studies on Ageing Group. Prevalence and European comparison of dementia in a ≥75‐year‐old composite population in Spain.
Acta Neurol Scand: 2011: 123: 316–324.
© 2010 John Wiley & Sons A/S. Objectives – To estimate dementia prevalence in Spain. Materials and methods – Nine probabilistic and geographically defined samples participated. A screening design based on the MMSE was implemented. Positively screened individuals underwent clinical evaluation. The total number of cases in Spain was estimated. Prevalence was confronted to that of other European countries. Results – Five hundred and forty‐six persons aged ≥75 participated, 49 had dementia (35 with Alzheimer’s disease [AD], 10 with vascular dementia [VD], 4 other; 25 first diagnosed in the study). Age‐ and sex‐adjusted prevalence and estimated nationwide cases were 7.5% (95% CI 5.4–9.7), 5.6 (95% CI 3.7–7.5) and 1.4 (95% CI 0.5–2.3), and 290,000 (95% CI 208,000–372,000), 214,000 (95% CI 141,000–288,000) and 54,000 (95% CI 20,000–88,000) for dementia, AD and VD, respectively. Conclusions – Dementia prevalence in Spain is comparable to other European populations, while a high number of undiagnosed cases live in the community. The potential impact of Mediterranean diet, hypertension control and decreasing vascular risk factors is discussed.     

Galantamine and behavior in Alzheimer disease: analysis of four trials

Kavanagh S, Gaudig M, Van Baelen B, Adami M, Delgado A, Guzman C, Jedenius E, Schäuble B. Galantamine and behavior in Alzheimer disease: analysis of four trials.
Acta Neurol Scand: 2011: 124: 302–308.
© 2011 John Wiley & Sons A/S. Objectives – Many individuals with Alzheimer’s disease (AD) experience behavioral and neuropsychiatric symptoms, which may cause caregiver distress and lead to the institutionalization of the patient. This analysis characterized behavioral symptoms and caregiver distress in trials of galantamine and their response to treatment. Materials and methods – Data were pooled from four randomized, placebo‐controlled clinical trials of galantamine in patients with mild to moderate AD (three studies) or AD plus cerebrovascular disease (one study) (n = 2177). Behavior and associated caregiver distress were assessed in each study using the Neuropsychiatric Inventory (NPI) and NPI distress (NPI‐D), respectively. Results – After 5/6 months, but not after 3 months, NPI score was significantly improved with galantamine vs placebo (P = 0.013). The benefit was particularly pronounced in patients categorized as having advanced moderate AD. At 5/6 months, there was a numerical benefit of galantamine over placebo in terms of caregiver distress; the difference was statistically significant in patients with moderate or advanced moderate AD. Conclusions – Galantamine reduces behavioral symptoms in patients with mild to moderate AD, leading to reduced caregiver burden. The reductions were greatest in patients with moderate or advanced moderate disease.     

EFNS guidelines for the diagnosis and management of Alzheimer’s disease

Background and objectives: In 2008 a task force was set up to develop a revision of the European Federation of the Neurological Societies (EFNS) guideline for the diagnosis and management of Alzheimer’s disease (AD) and other disorders associated with dementia, published in early 2007. The aim of this revised international guideline was to present a peer‐reviewed evidence‐based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with AD. Mild cognitive impairment and non‐Alzheimer dementias are not included in this guideline. Methods: The task force working group reviewed evidence from original research articles, meta‐analysis, and systematic reviews, published before May 2009. The evidence was classified and consensus recommendations graded (A, B, or C) according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. Results: The recommendations for clinical diagnosis, blood tests, neuropsychology, neuroimaging, electroencephalography, cerebrospinal fluid (CSF) analysis, genetic testing, disclosure of diagnosis, treatment of AD, behavioural and psychological symptoms in dementia, legal issues, counselling and support for caregivers were all revised as compared with the previous EFNS guideline. Conclusion: A number of new recommendations and good practice points are made, namely in CSF, neuropsychology, neuroimaging and reviewing non‐evidence based therapies. The assessment, interpretation, and treatment of symptoms, disability, needs, and caregiver stress during the course of AD require the contribution of many different professionals. These professionals should adhere to these guideline to improve the diagnosis and management of AD.     

Psychometric characteristics of the mini-mental state examination in patients with Alzheimer’s disease— a grade of membership analysis of cerad data: part II

In order to determine whether the Mini-Mental State Examination (MMSE) assesses multiple areas of cognitive functioning, a grade of membership analysis, carried out initially on data from a representative sample of community residents (see Part I), was repeated on data from 718 carefully characterized Alzheimer’s disease (AD) cases. The findings from both normal and demented samples differed little. In AD cases three pure types were identified which varied in level of cognitive impairment rather than by aspect of cognitive functioning. The presence of the originally proposed five aspects of cognitive functioning was not confirmed, although subsets (selected orientation items; three recall items; the two naming items) were identified. Nevertheless, since problems with learning and recall are a function of AD, and may underlie ability to respond to the items of the MMSE, summary MMSE score may be a sound indicator of severity of cognitive impairment, even if specific areas of cognitive functioning cannot be identified.