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Background: Our objective was to describe the frequency of behavioural and psychological symptoms of dementia (BPSD) in communitydwelling elderly adults with cognitive impairment and to determine whether these symptoms and behaviours assemble into distinct, clinically relevant categories. Methods: BPSD were measured using the Dysfunctional Behaviour Rating Instrument (DBRI). Principal components analysis was used to detect effects in caregiver responses in the DBRI. Results: The DBRI was scored on 921 patients. The frequency of individual BPSD ranged from 20% (spouse not spouse) to 83% (repeating questions). The frequency of BPSD increased with decline in cognitive function. Behaviours sorted into five broad domains: Anger, Delusions/ Paranoia, Withdrawn/Wandering, Agitation, and Repetitive Behaviours. Conclusions: BPSD are common in community-dwelling elderly persons with memory loss and may be aggregated into distinct, clinically relevant categories. [ABSTRACT FROM AUTHOR]

Background: Repeat cognitive testing is an essential diagnostic strategy to measure changes in cognition over time when following people with memory problems. Alternate forms may avert practice effects that can mimic improvements in cognition. We evaluated alternate forms of verbal fluency and logical memory (paragraph recall) tasks to evaluate their equivalence for clinical use.Methods: Participants with mild cognitive impairment (MCI) and dementia were recruited from five outpatient memory clinics and one nursing home. Participants with normal cognition (NC) were recruited from family members or friends. Verbal fluency categories of animals, cities & towns, fruits & vegetables and first names were used. Scores were recorded for 0-30 seconds, 31-60 seconds and errors. For the logical memory task, participants were read one of three different paragraphs and then were asked to recall the story. Immediate recall and delayed recall scores were recorded. The Standardized Mini-mental State Examination, the AB Cognitive Screen and the 15-point Geriatric Depression Scale were administered as part of the assessment. Analyses were performed using means, frequency distributions, t-tests, receiver-operating characteristic curves and effect sizes.Results: There were 46 NC participants, 45 with MCI and 55 with dementia. For verbal fluency, the mean number of animals, cities & towns, names or fruits & vegetables named in 60 seconds did not differ significantly within each cognitive group. First names was an easier category than the others: NC named 16.9-22.3 items, MCI named 11.6-14.4 items and dementia named 8.1-11.4 items. The mean number of items immediately recalled in logical memory was not significantly different for the three paragraphs. The verbal fluency task (in 60 seconds) and logical memory immediate recall were highly sensitive and specific to differences between NC and MCI (areas under the curves 0.87 and 0.76, respectively).Conclusions: Alternate forms allow serial testing without learning bias. Verbal fluency and logical memory tasks are sensitive to early cognitive changes. [ABSTRACT FROM AUTHOR]

Background: Depression is common in elderly people but physicians may not screen for it because of the length of time required by current screening instruments. We have developed a short screening instrument for depression for use in elderly people with normal cognition, mild cognitive impairment or early dementia.Methods: Participants were aged 55 years or more, had scored 20 or more on the standardized Mini-mental State Examination (SMMSE) and had been referred to a specialist geriatric outpatient memory clinic. Scores on the 30-item Geriatric Depression Scale (GDS) were analyzed. A composite GDS score, consisting of the top five individual question scores that correlated to depression (GDS >or= 14), were analyzed using a receiver operating curve analysis.Results: There were 810 patients with SMMSE scores of 20 or greater, of whom 202 (24.9%) scored 14 or more on the GDS, indicating depression. GDS question 16, "Do you often feel downhearted and blue?," had the highest correlation with the overall scores of 14 or more on the 30-point instrument (r = 0.64, p < 0.001). The next four questions with the highest correlates were Q10, "Do you often feel helpless?" (r = 0.56, p < 0.001), Q3, "Do you feel that your life is empty?" (r = 0.54, p < 0.001), Q9, "Do you feel happy most of the time?" (r = 0.52, p < 0.001), and Q1, "Are you basically satisfied with your life?" (r = 0.50, p < 0.001). The negative predictive value of "Do you often feel downhearted and blue?" answered negatively for depression was 96%. These five questions were used as a short screening instrument. The positive predictive value of four or five positive responses was 97%. These data were not significantly different whether the patient's SMMSE score was 20-25 or 26-30.Conclusions: The AB Clinician Depression Screen (ABCDS), comprising five questions, can rapidly identify patients with depression or eliminate that diagnosis. In this population, these five questions may be used instead of the longer 30-question GDS scale. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia. Methods 28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression. Results When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre ≥ 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre ≥ 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre ≥ 1:512 or IgA titre ≥ 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case – control) was – 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case – control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50. Conclusion We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia.

Objectives: Preliminary evidence suggested that doxycycline and rifampin might stop or slow the progression of Alzheimer's disease (AD). We carried out a randomized trial to confirm or refute these findings., Methods: A multicenter, blinded, randomized, 2 × 2 factorial controlled trial, set at 14 geriatric outpatient clinics in Canada. Four hundred and six patients with mild to moderate AD (standardized mini mental state examination (SMMSE) score 14-26) participated. The intervention was 12 months' treatment with doxycycline 100 mg twice daily + rifampin 300 mg daily or doxycycline 100 mg twice daily + placebo-rifampin daily or rifampin 300 mg daily + placebo-doxycycline twice daily or placebo-doxycycline twice daily + placebo-rifampin daily. Coprimary outcomes were the Standardized Alzheimer's Disease Assessment Scale-Cognitive Subscale (SADAS-cog) and the Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB). Secondary outcomes were the SMMSE, Quick mild cognitive impairment screen, Geriatric Depression Scale, Cornell Scale for Depression in Dementia, activities of daily living (Lawton Scale), and the Dysfunctional Behavior Rating Instrument frequency and reaction subscales., Results: There was a significant deterioration in SADAS-cog over time with both rifampin and doxycycline in comparison with placebo. When the two were used together, there was no statistically significant decline/deterioration in comparison with placebo (n = 305). For the CDR-SB, there were no significant effects of either rifampin or doxycycline. Secondary outcome results followed similar patterns., Conclusion: Twelve months' treatment with doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in AD., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: To determine the skeletal effects of alendronate therapy in men with primary hyperparathyroidism (PHPT) in comparison with those in postmenopausal women., Methods: There essentially are no published data on the effects of bisphosphonate therapy in men with PHPT. We previously conducted a double-blind, randomized, single- crossover trial of alendronate, 10 mg daily, in PHPT and reported that alendronate significantly increases bone mineral density (BMD) at 12 months relative to baseline values. That study sample included both women (n = 28) and men (n = 9) and both premenopausal (n = 4) and postmenopausal (n = 24) women. Study subjects were randomly assigned to receive either alendronate or placebo during the first year, and all subjects received alendronate during the second year. Among the men, 3 received alendronate and 6 received placebo during the first year. The current analysis focuses on the skeletal effects of alendronate therapy in the 9 men during their first year of treatment versus the 6 men during their first year while receiving placebo as well as the 24 postmenopausal women during their first year of alendronate therapy. Paired t tests comparing baseline and 12-month data were performed for the 9 treated men and the 6 control subjects; unpaired t tests were used to compare the 9 treated men and the 24 treated women., Results: Alendronate therapy for 1 year (n = 9) resulted in a 4.8% increase in BMD at the lumbar spine (P = .1) in comparison with the men who received 1 year of placebo (n = 6). Relative to baseline, men receiving alendronate showed a significant 4.4% gain in BMD at the lumbar spine (P = .009) and a 2.95% gain in total hip BMD (P =.027). A 47% decline in serum levels of bone-specific alkaline phosphatase activity was also noted with alendronate therapy (P = .003). Changes in BMD in the male population were similar to previously reported effects of alendronate therapy in postmenopausal women with PHPT., Conclusion: Alendronate therapy in men with PHPT is associated with improvements in BMD and reductions in bone turnover. These data, similar to the findings in postmenopausal women with PHPT, suggest that aminobisphosphonates may be of value in providing skeletal protection for men with PHPT. Further study is needed to confirm skeletal protection and fracture efficacy in this population.

There is epidemiological evidence suggesting an association between aluminum in drinking water and Alzheimer's disease (AD), and between aluminum in dialysate and dialysis dementia. The exact role of aluminum in the pathogenesis of these and other dementias is not clear. This study examined the acute effects of aluminum on cognitive function in patients with AD and related dementias and in age-matched and younger volunteers with normal cognitive function. Whether individuals with AD and/or the APOE epsilon4 genotype had enhanced gastrointestinal absorption of aluminum was tested, and whether individuals with elevated blood aluminum concentrations exhibited acute cognitive effects was determined. Subjects were randomized to receive a single dose of aluminum orally (Amphojel plus citrate) for 3 d followed by a 3-wk washout, and then 3 d of matched placebo administration, or vice versa. Serum aluminum levels were measured and the daily dose of Amphojel was adjusted to a target aluminum level between 50 and 150 microg/L. Neuropsychological tests were administered at baseline and 90 min after the third dose of Amphojel or placebo. There was a large interindividual variation in aluminum serum levels in all study groups after the same initial dose of Amphojel. There were no significant differences in neuropsychological test scores after aluminum ingestion in normal volunteers or in patients with cognitive impairment. There was no association between APOE epsilon4 genotype and aluminum absorption. The results did not support the hypothesis that aluminum ingested at these doses produces acute effects on cognition or adverse effects, nor did they reveal that AD patients are more vulnerable to such outcomes. Further inquiry is required to explore any possible association between aluminum and cognition, but controlled trials may be limited by safety concerns.

Background: Cognitive screening instruments are either too long for routine clinical use or not sensitive to distinguish mild cognitive impairment (MCI) from normal cognition (NC) or dementia., Objective: To evaluate the sensitivity and specificity of the AB Cognitive Screen (ABCS) and its subtests with a view to improving its ability to differentiate between dementia, MCI and NC. The influence of age and education on sensitivity and specificity is also examined., Design: Cross-sectional study., Methods: Participants with dementia and MCI were recruited from those presenting to four specialty geriatric clinics in southern Ontario. Participants with NC were recruited from the family and friends of patients. A comprehensive geriatric assessment was done including ABCS, SMMSE and 15 point Geriatric Depression Scale. Analysis of variance and receiver operating characteristic (ROC) curves compared test scores. SMMSE scores were also analysed for comparison purposes., Results: Three hundred and two participants had dementia, 166 had MCI and 174 had NC. ABCS total scores were significantly different between NC and MCI (mean difference 7.1, 1.8-12.5 CI, p = 0.000) while SMMSE scores were not (mean difference 0.5, -0.7-1.7, p < 0.628). Of individual ABCS subtests, verbal fluency and delayed recall were most sensitive to differences between NC and MCI. ROC curve analysis, which presents sensitivity and specificity, showed verbal fluency was better than delayed recall in distinguishing between NC and MCI, among participants 75 years of age or older., Conclusion: The AB Cognitive Screen (ABCS) can be administered in 3-5 min. The SMMSE and ABCS total and subtests significantly distinguished between dementia and MCI or NC. Verbal fluency and delayed recall were best at distinguishing between MCI and NC. The analysis illustrates how each subtest contributes to the sensitivity of the ABCS and suggests ways that sensitivity might be improved., ((c) 2006 John Wiley & Sons, Ltd.)

Objective: To compare the sensitivity and specificity of the AB Cognitive Screen (ABCS) with the Standardized Mini-Mental State Examination (SMMSE) to differentiate normal cognition from mild cognitive impairment (MCI), especially when educational level and age are taken into account., Method: This cross-sectional study took place at geriatric outpatient memory clinics. Participants were community-dwelling adults, aged 55 years or over, referred from primary care settings (a minority of participants were referred from specialists) for assessment of memory loss and age-matched control subjects with no complaint of memory loss. Each participant had the ABCS and the SMMSE administered in random order on the same day., Results: Participants included 124 patients diagnosed with MCI and 111 with normal cognitive function. The ABCS showed a statistically significant difference between normal cognition and MCI (ABCS score 111.7 and 104.6 points, respectively, P < 0.001) for the whole group. This difference was significant with the ABCS, regardless of participants' age or education. There was a significant difference between normal cognition and MCI for SMMSE scores (SMMSE score 27.8 and 27.2 points, respectively, P = 0.040), but the differences were not significant when age and education were taken into account. Age and education were shown to affect the scores of both instruments except for the ABCS scores of MCI subjects, which were not significantly affected by education (P = 0.059)., Conclusions: The ABCS is more sensitive than the SMMSE in differentiating normal cognition from MCI. The ABCS appears to be less influenced by education. It has improved clinical utility with a wider range of scoring gradations, reduced ceiling effects, and shorter scoring and administration times.

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

Cerebrolysin is a peptidergic drug which displays neurotrophic action in various animal models. It is used for the treatment of dementia and in this report we provide evidence for the long-term clinical efficacy of Cerebrolysin in Alzheimer's disease. This evidence is based on our clinical experience with Cerebrolysin, stemming from our participation in a double-blind, placebo-controlled clinical trial, a compassionate use programme initiated thereafter, and a PET study. Our data suggests, that Cerebrolysin is a safe and effective treatment for Alzheimer's disease and that repeat treatments may maintain function in patients over the long-term.

The Mini-Mental State Examination (MMSE) is a widely used screening test for cognitive impairment in older adults. Because the guidelines for its application are brief, the administration and scoring of the test can vary between different individuals. This can diminish its reliability. Furthermore, some of the items must be changed to accommodate different settings, such as the clinic, home, or hospital. Because there are no time limits, it is not clear how long one should wait for a reply to a question. It is also not clear how one deals with answers that are "near misses." The goal of the Standardized Mini-Mental State Examination (SMMSE) was to impose strict guidelines for administration and scoring to improve the reliability of the instrument. The reliability of the MMSE was compared with the reliability of the SMMSE in 48 older adults who had the tests administered by university students on three different occasions to assess the interrater and intrarater reliability of the tests. The SMMSE had significantly better interrater and intrarater reliability compared with the MMSE: The interrater variance was reduced by 76% and the intrarater variance was reduced by 86%. It took less time to administer the SMMSE compared with the MMSE (average 10.5 minutes and 13.4 minutes, respectively). The intraclass correlation for the MMSE was .69, and .9 for the SMMSE. Administering and scoring the SMMSE on a task-by-task basis are discussed.

Objectives: To compare the interrater and intrarater reliability of the Alzheimer's Disease Assessment Scale (ADAS) with the Standardized Alzheimer's Disease Assessment Scale (SADAS)., Design: A randomized, double blind trial. Sixteen university students were randomized to administer either version of the instrument. Subjects were randomized to three assessments, at 2-week intervals, using the ADAS or the SADAS. Each subject's first and third tests were administered by the same rater, the second by a different rater., Setting: A geriatric outpatient clinic in a university teaching hospital., Participants: Fifty-four patients with possible or probable Alzheimer's disease living in the community or in a long-term care facility., Measurements: The primary outcome was the interrater reliability of total ADAS and SADAS scores. Secondary outcomes were ADAS and SADAS cognitive scores, noncognitive scores, duration of testing, and sample size estimates., Results: The interrater reliability of the SADAS total score was significantly better than that of the ADAS (interrater ICC 0.93 SADAS vs 0.83 ADAS), and the interrater standard deviation of the total SADAS score was lower than that of the ADAS (38%, P < .05). The SADAS cognitive subscale inter and intrarater reliability, although higher than the ADAS, was not significantly different when used by different raters (interrater ICC 0.91 SADAS vs 0.90 ADAS; intrarater ICC 0.88 SADAS vs 0.86 ADAS). The SADAS noncognitive subscale was significantly more reliable than the ADAS (interrater ICC 0.89 SADAS vs 0.42 ADAS; intrarater ICC 0.87 SADAS vs 0.70 ADAS; P < or = .05) and had a lower standard deviation between raters (59%; P < .01) and within raters (40%; P < .05) compared with the ADAS., Conclusion: The improved reliability of the SADAS total score means that investigators can now use this score as a primary outcome measure, and important behavioral symptomatology can be included as a marker for treatment efficacy in AD. The smaller standard deviation of the SADAS means that clinical trials using the SADAS as a primary outcome will demonstrate differences, if present, with smaller sample sizes than with the ADAS.