Alzheimer Disease: Mayer LS

Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JC. · Khachaturian and Associates Inc., Potomac, MD, USA. · Arch Neurol. · Pubmed #16533956 links to  free full text

Abstract: BACKGROUND: Recent reports suggest that antihypertensive (AH) medications may reduce the risk of dementing illnesses. OBJECTIVES: To examine the relationship of AH medication use with incidence of Alzheimer disease (AD) among the elderly population (aged 65 years and older) of Cache County, Utah, and to examine whether the relationship varies with different classes of AH medications. METHODS: After an initial (wave 1) multistage assessment (1995 through 1997) to identify prevalent cases of dementia, we used similar methods 3 years later (wave 2) to identify 104 incident cases of AD among the 3308 survivors. At the baseline assessment, we obtained a detailed drug inventory from the study participants. We carried out discrete time survival analyses to examine the association between the use of AH medications (including angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) at baseline with subsequent risk of AD. RESULTS: Use of any AH medication at baseline was associated with lower incidence of AD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.41-0.98). Examination of medication subclasses showed that use of diuretics (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.94), and specifically potassium-sparing diuretics (adjusted hazard ratio, 0.26; 95% confidence interval, 0.08-0.64), was associated with the greatest reduction in risk of AD. Corresponding analysis with a fully examined subsample controlling for blood pressure measurements did not substantially change our findings. CONCLUSIONS: These data suggest that AH medications, and specifically potassium-sparing diuretics, are associated with reduced incidence of AD. Because the latter association is a new finding, it requires confirmation in further study.

Politis AM, Vozzella S, Mayer LS, Onyike CU, Baker AS, Lyketsos CG. · The Johns Hopkins University, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #15481065 No free full text.

Abstract: BACKGROUND: Apathy is a common symptom in patients with dementia and has adverse consequences for patients and caregivers. Most treatments for apathy, particularly non-pharmacologic interventions, have not been evaluated in controlled trials. OBJECTIVES: This study evaluated the efficacy of a kit-based activity intervention, compared to a time and attention control (one-on-one meetings with an activity therapist) in reducing apathy and improving quality of life in 37 patients with dementia. METHODS: The design was a randomized, controlled, partially masked clinical trial. All outcome measures were administered at baseline and follow-up. The primary outcome measure was the apathy score of the Neuropsychiatric Inventory (NPI). Other outcome measures were the NPI total score, the Alzheimer Disease Related Quality of Life scale(ADQRL), and the Copper Ridge Activity Index (CRAI). RESULTS: There was a significant reduction in NPI apathy scores in both treatment groups. The only significant difference between the two treatment groups was a modest advantage for the control intervention on the CRAI cueing subscale (p = 0.027), but not on the other CRAI subscales. There was also a greater within group improvement in quality of life ratings in the control intervention (p=0.03). CONCLUSIONS: Despite the substantial improvement in apathy scores during the course of the study, there was no clear advantage to the reminiscence-based intervention over the time and attention, one-on-one control intervention. More research is needed to develop specific behavioral interventions for apathy in patients with dementia.

Rosenblatt A, Samus QM, Onyike CU, Baker AS, McNabney M, Mayer LS, Brandt J, Lyketsos CG. · Department of Psychiatry and Behavioral Sciences, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #17676652 No free full text.

Abstract: OBJECTIVES: To describe patterns of Acetylcholinesterase inhibitor (ACI) use in an Assisted Living (AL) population, and the association of ACIs with retention in AL. METHODS: As part of the Maryland Assisted Living Study (MD-AL), 198 residents of 22 ALs were evaluated. Dementia was diagnosed in 134, and specifically Alzheimer's disease (AD) in 79, by an expert consensus panel. Data was collected on ACI agent and dose. Vital status and location were recorded every 6 months. Other data included age, duration of residence, general medical health rating (GHMR), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD) and number of non-psychiatric medications. RESULTS: The overall ACI treatment rate was 31%. 34.5% of participants with mild to moderate AD were taking ACIs. Only two in seven participants taking rivastigmine were taking an adequate dose. Participants with AD on ACI's did not differ significantly from those not on ACI's in any of the secondary measures except age and duration of residence, those on the agents being somewhat younger and more recently admitted. For participants with AD, only ACI use was significantly associated with retention in AL at 6 months, with a relative risk of death or discharge to higher level care of 0.217. Baseline MMSE was associated with retention for those with non-AD dementia. In a survival analysis ACI use was associated with 228.75 days longer retention in participants with AD. CONCLUSION: ACIs have low rates of use in AL and are associated with better retention for residents with AD.

Mayer LS, Bay RC, Politis A, Steinberg M, Steele C, Baker AS, Rabins PV, Lyketsos CG. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #16955427 No free full text.

Abstract: CONTEXT: Major depression affects about 25% of patients with Alzheimer's disease (AD) and has serious adverse consequences for patients as well as caregivers. Studies of treatments for depression in AD, like most treatment studies, depend on the ability of the scales used to measure outcome to detect a difference between the effects of treatment and control, particularly in trials conducted over waves. OBJECTIVE: To compare the ability of three depression scales, and some of their subscales, to detect the difference in the effects of drug (treatment) and placebo (control). DESIGN: Comparison of three scales of depression in terms of percent variance explained as indicated by the adjusted or partial eta-squared for the effect of drug versus placebo, controlling for baseline depression, in a randomized, placebo-controlled, parallel, 12-week, clinical trial of sertraline for the treatment of depression with AD. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four patients with probable Alzheimer's disease and Major Depressive Episode. OUTCOME MEASURES: The Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Neuropsychiatric-Inventory Mood Domains (NPI-M). RESULTS: Examination of the treatment effects as indicated by the partial eta-squared's for each scale at each wave, revealed a slight, but not significant, advantage for the use of the CSDD over the HDRS, and a significant advantage for the use of either of these over the NPI-M. Treatment effects, as reflected in the partial eta-squared's computed for the subscales at each wave, were significant for all four subscales, and were largest for the CSDD 'mood' subscale although they were not significantly greater than for the other subscales. CONCLUSIONS: The CSDD, and particularly its mood subscale, appears to be more sensitive than the HDRS, it's subscales or the NPI-M, for comparing drug to placebo in treating major depression in AD patients. Treatment effects as reflected in the partial eta-squared's were largest on the CSDD mood subscale and increased over time. The pattern for the other subscales was non-monotonic over waves and resembled the pattern for the entire scale. Perhaps combining the CSDD two subscales obscures the treatment effects for the separate subscales.

Khachaturian AS, Corcoran CD, Mayer LS, Zandi PP, Breitner JC, Anonymous00168. · Khachaturian and Associates Inc, Potomac, MD, USA. · Arch Gen Psychiatry. · Pubmed #15123497 links to  free full text

Abstract: BACKGROUND: The incidence of Alzheimer disease (AD) increases strongly with age, but little is known about the cumulative incidence of AD over a lifetime of 100 years, or its relationship to the polymorphic APOE locus that encodes apolipoprotein E. APOE is a strong genetic risk factor for AD. OBJECTIVES: To estimate the occurrence of AD as a function of age and number of APOE epsilon4 alleles; and to explore evidence for heterogeneity of AD risk related to APOE genotype and to other sources. DESIGN: Nonparametric and parametric survival analyses of AD incidence in prospective longitudinal study. SETTING AND PARTICIPANTS: A total of 3308 elderly residents of Cache County, Utah. MAIN OUTCOME MEASURES: Cumulative incidence of AD; in mixture models assuming susceptible and nonsusceptible individuals, the proportion of individuals not susceptible to AD at any age. RESULTS: Models that assumed a proportion of invulnerable individuals provided strongly improved fit to the data. These models estimated the 100-year lifetime incidence of AD at 72%, implying that 28% of individuals would not develop AD over any reasonable life expectancy. We confirmed the acceleration of AD onset in individuals with 1 or, especially, 2 APOE, epsilon4 alleles but observed no meaningful difference in 100-year lifetime incidence related to number of epsilon4 alleles. CONCLUSIONS: The APOE epsilon4 allele acts as a potent risk factor for AD by accelerating onset. However, the risk of AD appears heterogeneous in ways independent of APOE.Some individuals seem destined to escape AD, even over an extended lifespan. Their relative invulnerability may reflect other genes or environmental factors that can be investigated.

Politis AM, Mayer LS, Passa M, Maillis A, Lyketsos CG. · The Johns Hopkins University, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #15027034 No free full text.

Abstract: CONTEXT: No rating scales of the neuropsychiatric symptoms of patients with dementia and Alzheimer's disease (AD) have previously been developed or translated. OBJECTIVES: To develop a Hellenic translation of the Neuropsychiatric Inventory (NPI), to evaluate it's reliability and validity, and to compare NPI results in Greek patients referred to a neuropsychiatry clinic for either of two reasons: disturbing behaviors evoking embarrassment and disturbing behaviors evoking fear in the caregiver. METHODS: The Hellenic translations of the NPI, Brief Psychiatric Rating Scale (BPRS), and Emotional Distress Scale (EDS) were compared in evaluating 29 consecutive referrals of patients with AD. RESULTS: The Hellenic NPI (H-NPI) demonstrated a high degree of internal consistency reliability, and of concurrent validity when compared to the BPRS or the EDS. Patients referred for behaviors evoking embarrassment presented with higher scores on NPI ratings of apathy. However, patients referred for behaviors evoking fear presented with higher scores on NPI ratings of aggression and irritability. CONCLUSIONS: These results indicate that the H-NPI is a reliable instrument, able to detect differences in clinically referred groups of AD patients.

Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC, Anonymous00334. · Department of Mental Hygiene, School of Hygiene and Public Health, the Johns Hopkins University, Baltimore, Md, USA. · JAMA. · Pubmed #12413371 links to  free full text

Abstract: CONTEXT: Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. OBJECTIVE: To examine the relationship between use of HRT and risk of AD among elderly women. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. MAIN OUTCOME MEASURE: Diagnosis of incident AD. RESULTS: Thirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]). CONCLUSIONS: Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.