Vitamin D and risk of cognitive decline in elderly persons

Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, Ferrucci L, Melzer D; Archives of Internal Medicine 170 (13), 1135-41 (Jul 2010)

BACKGROUND: To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. METHODS: We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. RESULTS: The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels<25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. CONCLUSION: Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Treating Neuropsychiatric Symptoms in Dementia With Lewy Bodies: A Randomized Co

Culo S, Mulsant BH, Rosen J, Mazumdar S, Blakesley RE, Houck PR, Pollock BG; Alzheimer Disease & Associated Disorders (Jul 2010)

Sensitivity to psychotropic medications presents a therapeutic challenge when treating neuropsychiatric symptoms in patients with dementia with Lewy bodies (DLB). We compared under randomized, double-blinded conditions the tolerability and efficacy of citalopram and risperidone in the treatment of behavioral and psychotic symptoms in patients with DLB and Alzheimer disease (AD). Thirty-one participants with DLB and 66 with AD hospitalized for behavioral disturbance were treated under randomized, double-blind conditions with citalopram or risperidone for up to 12 weeks. Neuropsychiatric symptoms were assessed with the nursing home version of the Neuropsychiatric Inventory (NPI) and the Clinical Global Impression of Change (CGIC). Side effects were measured using the UKU Side Effect Rating Scale. A significantly higher proportion of participants with DLB (68%) than with AD (50%) discontinued the study prematurely. Discontinuation rates were comparable in DLB participants treated with citalopram (71%) or risperidone (65%). However, participants with DLB randomized to risperidone experienced a higher overall burden of side effects. Scores on the NPI and the CGIC worsened in DLB participants and improved in those with AD. Most patients with behavioral disturbances or psychosis associated with DLB tolerate citalopram or risperidone poorly and do not seem to benefit from either medication.

donepezil and apathy

Effect of donepezil on emergence of apathy in mild to moderate Alzheimer's disease; Waldemar G, Gauthier S, Jones R, Wilkinson D, Cummings J, Lopez O, Zhang R, Xu Y, Sun Y, Knox S, Richardson S, Mackell J; International Journal of Geriatric Psychiatry (Jul 2010)


OBJECTIVE: To determine whether donepezil treatment (10 mg/day over 24 weeks) is associated with delayed emergence of apathy in patients with mild to moderate Alzheimer's disease (AD) and to explore relationships between donepezil's effects on apathy and other Neuropsychiatric Inventory (NPI)-measured behavioural symptoms. METHODS: Two randomised, double-blind, parallel-group, placebo-controlled studies that met prespecified criteria and were sufficiently similar to allow data pooling were derived from all donepezil AD clinical trials. Patients scoring from 10 to 26 on baseline Mini-Mental Status Examination were included. A clinical milestone for apathy and other NPI items was defined as the first emergence of a composite score (frequency x severity)>/=3. Differences in time to event (i.e. milestone) between donepezil- and placebo-treated groups were assessed using the Kaplan-Meier method and log-rank test. Shift tables were constructed to evaluate clinical milestone status for apathy and other NPI items at baseline and endpoint, and were analysed using the Cochran-Mantel-Haenszel (CMH) test, stratified by baseline status. RESULTS: Of all NPI items, apathy had the highest proportion of subjects scoring>/=3 at baseline. Donepezil was superior to placebo on both apathy milestone analyses (time-to-event log-rank test and shift table CMH test, p = 0.01). Aberrant motor behaviour demonstrated similar benefit. CONCLUSIONS: Donepezil treatment appears to have resulted in a significant reduction over 6 months of the emergence of apathy in patients with AD. These data suggest that a prospective clinical trial in patients with early AD that includes apathy as a primary outcome measure may be warranted. Copyright (c) 2010 John Wiley&Sons, Ltd.

Cholinesterase inhibitor minutiae

1.  oral donepezil is not affected by food, unlike rivastigmine and galanthamine
2.  donepezil has 3-5 hours to peak onnset v. 0.5-1 for galanthamine and rivastigmine (oral) and 8-10 hours for rivastigmine patch
3. serum half life is 70-80 hours for oral donepezil, 5-7 hours for galantamine, 2-8 hours for oral rivastigmine, 3-4 hours for rivastigmine patch and 60-80 hours for memantine

GOVERNMENT REPORT ON RISK FACTORS FOR ALZ DISEASE

http://www.ahrq.gov/downloads/pub/evidence/pdf/alzheimers/alzcog.pdf

 

UPSHOT

GOOD:  PHYSICAL ACTIVITY, COGNITIVE ENGAGEMENT

BAD; SMOKING, E4 ALLELE, DIABETES,HYPERTENSION

 

LONG REPORT IF YOU WANT DETAILS.

Frontotemporal dementia- clinical pearls

1.  Frontotemporal dementia is a clinical term, frontolobar degeneration is a pathologic term

2.  Preservation of memory, ability to keep track of day events, timing of spouse coming to and leaving home, and lack of getting lost (intact visuospatial) are characteristic, as is young age at onset (is second most common presentation before age 65, third after).

3. FTD-bv is more common than FTD-lang presentation.  See other post for criteria.  Presentation of FTD-bv includes difficulty with modulating behaviors (disinhibition, perseveration, lack of initiative), personality change, emotional blunting and loss of insight.  Language presentation  can be a problem with expression and naming, or word meaning (semantic dementia).  Later, dementia becomes more global.  Patients have frontal lobe release signs and in some cases, evidence of MND or Parkinson's. 

4.  Web resources
www.ftd-picks.org
www.aphasia.org