Alendronate therapy in men with primary hyperparathyroidism.

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.

Alternate forms of logical memory and verbal fluency tasks for repeated testing in early cognitive changes.

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.

Do the ABCS 135 short cognitive screen and its subtests discriminate between normal cognition, mild cognitive impairment and dementia?

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.

A short screen for depression: the AB Clinician Depression Screen (ABCDS).

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.

Screening for mild cognitive impairment: comparing the SMMSE and the ABCS.

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.

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial.

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.