A Mini-Mental State Examination Formula May Help to Distinguish Alzheimer's Disease from Dementia with Lewy Bodies.

BACKGROUND: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) differ in their memory, attention, and visuoconstructional characteristics. The subscales of the well-known Mini-Mental State Examination (MMSE) provide an opportunity to assess these characteristics. Previous research has shown that analysis of the MMSE subscale performance of AD and DLB patients helps to differentiate them. OBJECTIVE: Study the MMSE scores of AD and DLB patients to see if the ability of previously reported analyses to differentiate them could be improved. Include other dementia patients for perspective. METHODS: We studied the MMSEs of all patients seen in our clinics during an 18-month period. Different equations were studied, derived from the subscales of Memory (M, 3 points maximum), Attention (A, 5 points maximum), and Pentagon-copying (P, 1 point maximum). RESULTS: We obtained 400 MMSEs, 136 from AD patients and 24 from DLB patients, scoring range 1-30. The equation P minus M provided the best discrimination between AD and DLB. Using a P-M score = 1 to identify AD, the positive predictive value was 0.97, negative predictive value 0.22, specificity 0.92, and sensitivity 0.43. As a secondary finding, the P-M = 1 equation was also helpful to differentiate AD from Parkinson's disease dementia. CONCLUSION: Considering AD versus DLB in our clinic population, a demented patient who was unable to recall the three memory words on the MMSE but able to copy the intersecting pentagons had a 97% likelihood of having AD. Additional work is needed to improve the sensitivity of the P-M = 1 equation.

Donepezil May Reduce Insulin-Like Growth Factor-1 (IGF-1) Levels in Alzheimer's disease.

OBJECTIVE: Determine if donepezil will raise the insulin-like growth factor-1 levels of patients with amnestic mild cognitive impairment and Alzheimer's disease. DESIGN: In an outpatient setting, recruit amnestic mild cognitive impairment and Alzheimer's disease patients who were to start treatment with donepezil. Measure total serum insulin-like growth factor-1 levels before and after 3-6 months of treatment. RESULTS: Twenty-four patients were recruited. After a mean duration of 129 ± 37 days, 14 patients returned taking 5 mg (n=4) or 10 mg (n=10) donepezil per day. Twelve patients experienced decreases in their insulin-like growth factor-1 levels, one had no change, and one experienced an increase. Their mean insulin-like growth factor-1 level dropped by 13%, from 113 ± 31 ng/ml to 98 ± 28 ng/ml (p<0.001). CONCLUSION: Contrary to the expected increase in insulin-like growth factor-1 levels in response to donepezil that has been reported for normal elderly adults, our patients experienced decreases. This finding suggests that the somatotropic axis is altered in amnestic mild cognitive impairment and Alzheimer's disease relative to normal older adults.

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial.

OBJECTIVE: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. METHODS: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). RESULTS: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. CONCLUSIONS: Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect.

A validity study of the Working Group's Autobiographical Memory Test for individuals with moderate to severe intellectual disability.

The purpose of the present study was to investigate the validity of the Working Group's Autobiographical Memory Test as a dementia screening tool for individuals with moderate to severe intellectual disabilities (ID). Twenty-one participants with Dementia of Alzheimer's Type (DAT) and moderate to severe ID and 42 controls with similar levels of ID were tested. The majority were re-tested one year after the initial evaluation. The DAT group scored considerably lower than the control group on the initial evaluation. The controls with DS exhibited a considerable decline on the follow-up evaluation whereas other participants exhibited little changes. This demonstrates an insignificant overall difference between the DAT group and the control group on the follow-up evaluation. Virtually all participants exhibited the same scores on 3 out of 6 test items and the percentage of participants who correctly answered the remaining three test items were not significantly different from the DAT or control groups. In conclusion, the Working Group's Autobiographical Memory Test may be useful as a dementia screening tool for individuals with moderate to severe ID from DS when validated with a large sample size study. However, it is questionable whether this test is a reliable dementia screening tool for individuals with moderate to severe ID from non-DS etiologies. This test has a significant psychometric weakness because of the restricted score variability among the participants.

Is brain amyloid production a cause or a result of dementia of the Alzheimer's type?

The amyloid cascade hypothesis has guided much of the research into Alzheimer's disease (AD) over the last 25 years. We argue that the hypothesis of amyloid-ß (Aß) as the primary cause of dementia may not be fully correct. Rather, we propose that decline in brain metabolic activity, which is tightly linked to synaptic activity, actually underlies both the cognitive decline in AD and the deposition of Aß. Aß may further exacerbate metabolic decline and result in a downward spiral of cognitive function, leading to dementia. This novel interpretation can tie the disparate risk factors for dementia to a unifying hypothesis and present a roadmap for interventions to decrease the prevalence of dementia in the elderly population.

A pilot study of a test for visual recognition memory in adults with moderate to severe intellectual disability.

Objective assessment of memory functioning is an important part of evaluation for Dementia of Alzheimer Type (DAT). The revised Picture Recognition Memory Test (r-PRMT) is a test for visual recognition memory to assess memory functioning of persons with intellectual disabilities (ID), specifically targeting moderate to severe ID. A pilot study was performed to investigate whether the r-PRMT could differentiate DAT-related memory decline from pre-existing poor memory functioning of persons with moderate to severe ID. The r-PRMT scores were compared between 26 participants with DAT and moderate to severe ID and 33 controls with similar levels of ID. The results revealed that the controls with DS showed uniformly high scores in contrast to those with DAT on the r-PRMT and the score distributions of two groups were distinctly different with no overlap. On the other hand, the controls with non-DS etiologies scored much lower with a wider score spread, resulting in significant overlap with the score distribution of the participants with DAT. In conclusion, the r-PRMT may be effective in identifying persons with DAT among persons with moderate to severe ID from DS. However, the r-PRMT may result in a high false positive error rate in discriminating those with DAT among persons with moderate to severe ID from non-DS etiologies, if the judgment is based on a single point assessment.