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author:("wessels, K")
1.  Nicotine treatment of mild cognitive impairment 
Neurology  2012;78(2):91-101.
To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI).
Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings.
Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent.
This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies.
Classification of evidence:
This study provides Class I evidence that 6 months of transdermal nicotine (15 mg/day) improves cognitive test performance, but not clinical global impression of change, in nonsmoking subjects with amnestic MCI.
PMCID: PMC3466669  PMID: 22232050
2.  Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies 
Levodopa (L‐dopa) is the gold standard treatment for Parkinson's disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L‐dopa use in patients with parkinsonism and dementia. Therefore, the effect of L‐dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unclear.
To ascertain the acute and long‐term effects of L‐dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson's disease.
Baseline cognitive and motor function was assessed off L‐dopa in patients with Parkinson's disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L‐dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L‐dopa to assess the prolonged effect.
Acute L‐dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson's disease both with and without dementia on L‐dopa at 3 months. Although patients with Parkinson's disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L‐dopa treatment.
The use of L‐dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.
PMCID: PMC2077405  PMID: 16952917
3.  Attentional deficits affect activities of daily living in dementia‐associated with Parkinson's disease 
To investigate the effects of attentional deficits on activities of daily living (ADL) in patients with dementia associated with Parkinson's disease (PDD).
461 patients were assessed neuropsychologically. Factor analyses were used to differentiate attention from other cognitive functions and to differentiate different aspects of ADL functions. The effects of the attentional measure on ADL were examined using sequential multiple regression, controlling for age, sex, education, severity of motor symptoms and other cognitive functions.
Three cognitive factors were identified, with one factor emerging as a measure of vigilance and focused attention. This factor predicted different aspects of ADL status even after controlling for motor functions and other cognitive factors. The attention factor was the single strongest cognitive predictor of ADL status, matching the strength of the effects of motor functions on ADL status.
Impaired attention is an important determinant of ADL functions in patients with PDD.
PMCID: PMC2077544  PMID: 16801351
5.  A pilot study of the effect of low level exposure to mercury on the health of dental surgeons. 
OBJECTIVES--This project was conducted to examine whether the computerised analysis of psychomotor responses available from Cognitive Drug Research is appropriate for measuring an effect of low level exposure to mercury in dentists. METHODS--A computerised battery of psychomotor tests was given to two groups of dentists (older dentists and trainees) and to two age matched control groups. As well as the psychomotor tests, volunteers were required to complete a questionnaire to identify potential influences on psychomotor performance and to provide a sample for analysis of urinary mercury. RESULTS--Statistical analysis of the results showed that the older dentists had slightly higher concentrations of urinary mercury although most were around background levels and they were all within occupational limits. Five of the psychomotor tests showed no differences between the performance of the four groups. The older dentists showed significantly better performance on the simple reaction time test and significantly poorer performance in the immediate word recall and delayed word recall tests. CONCLUSIONS--Poorer performance in memory recall tests confirms previously reported studies. This together with the confirmation that this test system is a practical tool in the occupational setting suggests that a larger study of the effects of mercury exposure on dentists would be appropriate.
PMCID: PMC1128382  PMID: 8563844
6.  Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study 
European Journal of Neurology  2014;22(1):106-e7.
Background and purpose
Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.
Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles.
Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06–2.60, P = 0.03; 1.62, 95% confidence interval 1.02–2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication.
Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.
PMCID: PMC4310141  PMID: 25117780
attention; cognitive decline; cohort study; 25-hydroxyvitamin D

Results 1-6 (6)