Alzheimer Disease: Cummings J

McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M, Anonymous00346. · Institute for Ageing and Health, University of Newcastle upon Tyne, UK. · Neurology. · Pubmed #16237129 No free full text.

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Fillit H, Cummings J. · Mount Sinai Medical Center, New York City, USA. · Manag Care Interface. · Pubmed #10747691 No free full text.

Abstract: The progressive loss of social and physical functioning associated with Alzheimer's disease (AD) results in extensive social and economic costs to society. The early diagnosis and treatment of AD may reduce cognitive and behavioral symptoms of this disease and may slow disease progression, thereby alleviating some of these social and economic costs. The Alzheimer's Disease Managed Care Advisory Council, a panel of experts from managed care, academic medicine, and the Los Angeles chapter of the Alzheimer's Association was convened to synthesize current evidence-based recommendations for AD diagnostic and treatment guidelines and to integrate these guidelines for use in MCOs. This paper presents conclusions from this panel and provides an algorithm for the treatment of AD specifically for managed care settings. When combined with other necessary efforts to educate providers, these guidelines should improve the cost-effectiveness and quality of care for individuals with dementia in managed care.

Cummings J. · No affiliation provided · Can J Neurol Sci. · Pubmed #16583716 No free full text.

This publication has no abstract.

Weintraub S, Salmon D, Mercaldo N, Ferris S, Graff-Radford NR, Chui H, Cummings J, DeCarli C, Foster NL, Galasko D, Peskind E, Dietrich W, Beekly DL, Kukull WA, Morris JC. · Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, 320 E. Superior, Searle 11-467, Chicago, IL 60611, USA. · Alzheimer Dis Assoc Disord. · Pubmed #19474567 No free full text.

Abstract: The neuropsychologic test battery from the Uniform Data Set (UDS) of the Alzheimer's Disease Centers (ADC) program of the National Institute on Aging consists of brief measures of attention, processing speed, executive function, episodic memory, and language. This paper describes development of the battery and preliminary data from the initial UDS evaluation of 3268 clinically cognitively normal men and women collected over the first 24 months of utilization. The subjects represent a sample of community-dwelling, individuals who volunteer for studies of cognitive aging. Subjects were considered "clinically cognitively normal" based on clinical assessment, including the Clinical Dementia Rating scale and the Functional Assessment Questionnaire. The results demonstrate performance on tests sensitive to cognitive aging and to the early stages of Alzheimer disease in a relatively well-educated sample. Regression models investigating the impact of age, education, and sex on test scores indicate that these variables will need to be incorporated in subsequent normative studies. Future plans include: (1) determining the psychometric properties of the battery; (2) establishing normative data, including norms for different ethnic minority groups; and (3) conducting longitudinal studies on cognitively normal subjects, individuals with mild cognitive impairment, and individuals with Alzheimer disease and other forms of dementia.

Farlow MR, Cummings J. · Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Dement Geriatr Cogn Disord. · Pubmed #18311077 No free full text.

Abstract: BACKGROUND/AIMS: Parkinson's disease dementia (PDD) is common, but its neuropathological basis has been controversial. The aim of this review was to survey the recent literature on the pathology of PDD and compare the pathology of PDD to that of Alzheimer's disease (AD). METHODS: A literature search was performed to identify relevant research published since 2001. RESULTS: There is widespread Lewy body pathology in the neocortex and subcortical regions in PDD, and Lewy neurites in the CA2 region of the hippocampus that correlate with cognitive decline. Genetic forms of PD, which frequently lead to dementia, are associated with deposition of alpha-synuclein; PDD is not related to the apolipoprotein E epsilon 4 genotype. Compared with AD, central cholinergic deficits occur earlier, are greater and more widespread in PDD, but PDD can occur without the abundant senile plaques and neurofibrillary tangles indicative of AD. CONCLUSION: Epidemiological investigations, neuroimaging, as well as genetic and neuropathological studies increasingly support PDD as distinct from AD.

Cummings J, Winblad B. · UCLA Alzheimer's Center, 10911 Weyburn Avenue, Suite 200, Los Angeles, CA 90095-7226, USA. · Expert Rev Neurother. · Pubmed #17997695 No free full text.

Abstract: Rivastigmine patch is the first transdermal treatment to be approved for Alzheimer's disease (AD) and Parkinson's disease dementia in the USA and for AD in Europe. It provides smooth, continuous drug delivery, and has the potential to maintain rivastigmine concentrations within an optimal therapeutic window while avoiding the peaks and troughs associated with oral drug delivery. The target dose, rivastigmine 9.5 mg/24 h patch (a 10 cm(2) patch), is given once daily and requires a simple one-step dose titration to the therapeutic dose. In a 24-week study in 1195 AD patients, the rivastigmine 9.5 mg/24 h patch provided similar efficacy to the highest dose range of capsules, with approximately three-times fewer reports of nausea and vomiting. Patients in the 9.5 mg/24 h patch and 12 mg/day capsule groups evidenced significant improvements versus placebo on both primary outcome measures: the Alzheimer's Disease Assessment Scale-Cognitive subscale; and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change; in addition to the following secondary outcome measures: Alzheimer's Disease Cooperative Study-Activities of Daily Living scale; Mini-Mental State Examination; and Trail Making Test Part A for assessment of attention, visual tracking and motor processing speed. Treatment differences on the Neuropsychiatric Inventory and Ten Point Clock-drawing Test did not reach statistical significance in this study. The patch may be the optimal way to treat dementia patients with rivastigmine.

Cummings J, Lefèvre G, Small G, Appel-Dingemanse S. · UCLA Alzheimer's Center, Los Angeles, CA 90095-7226, USA. · Neurology. · Pubmed #17646618 No free full text.

Abstract: The dual cholinesterase inhibitor rivastigmine is approved in capsule form in many countries for the symptomatic treatment of dementia associated with Alzheimer disease (AD) and Parkinson disease (PD). All orally administered cholinesterase inhibitors are associated with central cholinergic gastrointestinal side effects, particularly during the titration phase, which are believed to be caused by a rapid increase in brain acetylcholine levels after effective inhibition of the target enzymes. A recently developed rivastigmine transdermal patch may have the potential to reduce such side effects. Pharmacokinetic studies have shown that transdermal administration of rivastigmine prolongs t(max), lowers C(max), and reduces fluctuations in plasma concentration. The 10-cm(2) rivastigmine patch provides comparable exposure (area under the curve, AUC) to the highest capsule dose (6-mg BID) and may be the target maintenance dose for most patients, delivering optimal rivastigmine exposure to produce a therapeutic effect. The potential of a patch to improve the tolerability of rivastigmine (e.g., nausea and vomiting) while permitting similar exposure to the highest doses of capsules may, in turn, lead to improved efficacy and compliance.

Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. · INSERM U610, Hôpital de la Salpêtrière, Paris, France. · Lancet Neurol. · Pubmed #17616482 No free full text.

Abstract: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, Inzitari D, Orgogozo JM, Sauer H, Scheltens P, Scarpini E, Herrmann N, Farlow M, Potkin S, Charles HC, Fox NC, Lane R. · Division of Neurology, University of British Columbia Hospital, Vancouver, Canada. · Lancet Neurol. · Pubmed #17509485 No free full text.

Abstract: OBJECTIVE: To assess the effect of rivastigmine in patients with mild cognitive impairment (MCI) on the time to clinical diagnosis of Alzheimer's disease (AD) and the rate of cognitive decline. METHODS: The study was a double-blind, randomised, placebo-controlled trial of up to 48 months. All patients had MCI operationally defined by having cognitive symptoms, a global clinical dementia rating stage of 0.5, a score of less than 9 on the New York University delayed paragraph recall test, and by not meeting the diagnostic criteria for AD. Primary efficacy variables were time to clinical diagnosis of AD, and change in performance on a cognitive test battery. This study is registered with the US National Institutes of Health clinical trials database (ClinicalTrials.gov), number NCT00000174. FINDINGS: Of 1018 study patients enrolled, 508 were randomly assigned to rivastigmine and 510 to placebo; 17.3% of patients on rivastigmine and 21.4% on placebo progressed to AD (hazard ratio 0.85 [95% CI 0.64-1.12]; p=0.225). There was no significant difference between the rivastigmine and placebo groups on the standardised Z score for the cognitive test battery measured as mean change from baseline to endpoint (-0.10 [95% CI -0.63 to 0.44], p=0.726). Serious adverse events were reported by 141 (27.9%) rivastigmine-treated patients and 155 (30.5%) patients on placebo; adverse events of all types were reported by 483 (95.6%) rivastigmine-treated patients and 472 (92.7%) placebo-treated patients. The predominant adverse events were cholinergic: the frequencies of nausea, vomiting, diarrhoea, and dizziness were two to four times higher in the rivastigmine group than in the placebo group. INTERPRETATION: There was no significant benefit of rivastigmine on the progression rate to AD or on cognitive function over 4 years. The overall rate of progression from MCI to AD in this randomised clinical trial was much lower than predicted. Rivastigmine treatment was not associated with any significant safety concerns.

Gauthier S, Loft H, Cummings J. · MCSA Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, Quebec, Canada. · Int J Geriatr Psychiatry. · Pubmed #18058838 No free full text.

Abstract: INTRODUCTION: Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD. METHODS: Data were pooled from six 24/28-week, randomised, placebo-controlled, double-blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20 mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single-item scores at weeks 12 and 24/28. RESULTS: At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p=0.001 and p=0.008), and in NPI single items: delusions (p=0.007 week 12, p=0.001 week 24/28), hallucinations (p=0.037 week 12), agitation/aggression (p=0.001 week 12, p=0.001 week 24/28), and irritability/lability (p=0.005 week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p=0.002), delusions (p=0.047), and disinhibition (p=0.011), at week 12, and of agitation/aggression (p=0.002), irritability/lability (p=0.004), and night-time behaviour (p=0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results. CONCLUSIONS: The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care.

Kurlan R, Cummings J, Raman R, Thal L, Anonymous00094. · Mt. Hope Professional Building, Rochester, NY 14620, USA. · Neurology. · Pubmed #17452579 No free full text.

Abstract: OBJECTIVE: To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism. METHODS: Multicenter randomized, double-blind, placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n = 8). The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was change in the Unified PD Rating Scale (UPDRS) motor section over the same time period. The trial was confounded by the need for a design change and incomplete recruitment. RESULTS: No significant differences in the primary or secondary outcome measures of efficacy were observed. An unexpectedly large placebo effect, inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not worsen parkinsonism, but was associated with a trend toward a decline on a measure of daily functioning. CONCLUSIONS: Quetiapine was well-tolerated and did not worsen parkinsonism. Although conclusions about efficacy may be limited, the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism. These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients.

Winblad B, Cummings J, Andreasen N, Grossberg G, Onofrj M, Sadowsky C, Zechner S, Nagel J, Lane R. · Karolinska Institutet Alzheimer Research Center, Stockholm, Sweden. · Int J Geriatr Psychiatry. · Pubmed #17380489 No free full text.

Abstract: OBJECTIVES: To compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD). METHODS: In this 24-week, multicenter, double-blind, double-dummy, placebo- and active-controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm(2) (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study--Clinical Global Impression of Change (ADCS-CGIC). RESULTS: One thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS-Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p=0.005), 2.6 (p<0.001) and 1.6 (p=0.003). Treatment differences on the ADCS-CGIC were 0.3 (p=0.01), 0.2 (p=0.054) and 0.3 (p=0.009). Comparison between the 10 cm2 patch and the capsule revealed non-inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in<or=10% patients across the four patch sizes (5, 10, 15 and 20 cm2). CONCLUSIONS: The target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients.

Ferris SH, Aisen PS, Cummings J, Galasko D, Salmon DP, Schneider L, Sano M, Whitehouse PJ, Edland S, Thal LJ, Anonymous00336. · Alzheimer's Disease Center, New York University School of Medicine, New York, NY 10016, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17135805 No free full text.

Abstract: One objective of the Alzheimer's Disease Cooperative Study (ADCS) is to develop new or improved instruments and assessment methods for evaluating treatment efficacy in Alzheimer disease (AD) clinical trials. The ADCS Instrument Committee has previously helped to define the state of the art in assessment for AD and Mild Cognitive Impairment clinical trials. We are now entering an exciting era of primary prevention trials to evaluate promising treatments that may delay disease onset and there is a need to develop appropriate instruments for these trials. The ADCS instrument committee has undertaken a project to develop instruments for prevention studies that assess domains known to be important in AD. Prevention trials are long and require large numbers of subjects, making them costly and requiring a high burden of participation for subjects. The current study focused on developing instruments that can be completed at home and in the clinic. The instruments are being evaluated in a cohort of nondemented elderly participating in a 4-year longitudinal study that simulates the design of a primary prevention trial. This report describes the design, baseline characteristics, and some longitudinal outcomes of the study cohort through the completion of the first 2 years of follow-up. We also describe the assessment domains to be measured with our new experimental instruments. This study recruited 644 subjects, 75 years of age and older. Participation in a "book club" that provided free books of interest to elders was offered as a recruitment incentive. Approximately 23% had some mild cognitive symptoms consistent with a Clinical Dementia Rating of 0.5. All subjects received a standardized in-clinic evaluation at baseline, which is repeated annually for 4 years to identify cases suspected of developing dementia and to measure longitudinal change on established clinical assessments. Subjects completed a set of self-administered experimental instruments at home or in the clinic designed to assess cognitive function and behavior, global change, activities of daily living, quality of life, and resource use. An additional "mail-in cognitive function questionnaire" was obtained separately by mail, 1 month before the other assessments. To evaluate the feasibility, efficiency, and validity of the home-based instruments in comparison with acquiring the same information during a clinic visit, subjects were randomized to 1 of 2 conditions in which the baseline and annual follow-up assessments are completed either at home ("home group") or at the study site during their clinic visits ("clinic group"). This initial report describes the ongoing 4-year longitudinal study and provides baseline results, which confirm the feasibility of obtaining home-based clinical information via mail or telephone. Initial results for the experimental instruments and for the book club are reported in separate accompanying articles.

Sano M, Egelko S, Jin S, Cummings J, Clark CM, Pawluczyk S, Thomas RJ, Schittini M, Thal LJ, Anonymous00303. · Mount Sinai School of Medicine, Bronx, NY, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17132967 No free full text.

Abstract: OBJECTIVE: To evaluate the feasibility of longitudinal assessment and the psychometric properties of both established and new outcome measures used in clinical trials of patients with dementia in a cohort of Spanish-speaking elders in the United States. METHODS: This is a prospectively collected multicenter study comparing patients with Alzheimer disease (AD) (N=77) and elderly controls (N=17) who are primary Spanish speakers. Spanish-speaking individuals with AD (SSI AD) were selected to represent predefined categories of impairment as determined by a Mini-Mental State Examination score. Controls were selected to approximately match by age and education (SSI C). Subjects were administered a series of Spanish translations of established outcome measures (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Dementia Scale), and Functional Assessment Staging (FAST)] and new outcome measures developed for United States in clinical trials to assess cognition, function, behavioral disturbance, and clinical global change. Half of the subjects were assessed at 1 and 2 months to evaluate reliability; all subjects were assessed at 6 and 12 months. Comparisons were made between patients and controls and between the Spanish-speaking cohort and a similar English-speaking cohort. RESULTS: The 12-month completion rate was 77%, with a trend toward greater impairment in those with full retention. Both established and new measures demonstrated good internal consistency and test-retest reliability in this cohort. All but one measure of cognition demonstrated excellent discriminability between AD subjects and controls. The SSI AD cohort declined significantly on measures of cognition, function, and clinical global change over the 12-month assessment period. The SSI AD and English AD (ESI AD) cohorts declined equivalently on the most common outcomes in clinical trials of AD (delayed recall, clinical global change). Likewise, the most common behavioral changes were also similar in the ESI and SSI groups. However, the annual change was lower in SSI AD than in the ESI AD on several other measures of cognition and function. CONCLUSIONS: These results support the recruitment of Spanish-speaking patients and the use of Spanish language translations for use in the clinical trials for AD.

Morris JC, Weintraub S, Chui HC, Cummings J, Decarli C, Ferris S, Foster NL, Galasko D, Graff-Radford N, Peskind ER, Beekly D, Ramos EM, Kukull WA. · Washington University, St. Louis, MO 63108, USA. · Alzheimer Dis Assoc Disord. · Pubmed #17132964 No free full text.

Abstract: A Clinical Task Force, composed of clinical leaders from Alzheimer's Disease Centers (ADC), was convened by the National Institute on Aging to develop a uniform set of assessment procedures to characterize individuals with mild Alzheimer disease and mild cognitive impairment in comparison with nondemented aging. The resulting Uniform Data Set (UDS) defines a common set of clinical observations to be collected longitudinally on ADC participants in accordance with standard methods. The UDS was implemented at all ADCs on September 1, 2005. Data obtained with the UDS are submitted to the National Alzheimer's Coordinating Center and represent a unique and valuable source of data to support and stimulate collaborative research.

Maurer K, McKeith I, Cummings J, Ames D, Burns A. · Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt on Main, Frankfurt, Germany. · Lancet. · Pubmed #17084762 No free full text.

This publication has no abstract.

Morris JC, Cummings J. · Washington University School of Medicine, 4488 Forest Park Avenue, Suite 130, St. Louis, Missouri 6108, USA. · J Alzheimers Dis. · Pubmed #16006667 No free full text.

This publication has no abstract.

Back-Madruga C, Boone KB, Briere J, Cummings J, McPherson S, Fairbanks L, Thompson E. · University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA. · Clin Neuropsychol. · Pubmed #12607146 No free full text.

Abstract: A frontal, or executive, variant of Alzheimer's disease (EAD) has been described in the literature in which frontal dysfunction accompanies temporal and parietal changes in the early stages of the illness. However, no study has empirically investigated associated aspects, such as neuropsychiatric symptoms, instrumental activities of daily living, or caregiver burden in this EAD subgroup. We compared the performance of two subgroups of mild Alzheimer's disease patients (e.g., EAD and typical Alzheimer's disease; TAD) on neuropsychological and associated measures. Results revealed that the EAD group, selected based on poor executive scores, did not significantly differ from the TAD group on nonexecutive neuropsychological tests of intelligence, language, verbal and nonverbal memory, or visual-spatial abilities. However, the EAD group evidenced more severe neuropsychiatric symptoms, impaired activities of daily living, and greater caregiver distress than the TAD group. Thus, the EAD subgroup is characterized by executive dysfunction, neuropsychiatric symptoms, and functional disability in excess of that seen in TAD. Whether our EAD subgroup represents an actual frontal variant of Alzheimer's disease awaits replication in a larger sample including neuroimaging and pathological confirmation, as well as longitudinal assessment of cognition and neuropsychiatric symptoms.

Bartzokis G, Sultzer D, Cummings J, Holt LE, Hance DB, Henderson VW, Mintz J. · Department of Psychiatry, University of Arkansas for Medical Sciences and the Mental Health Service, Central Arkansas Veterans Healthcare System, Little Rock, USA. · Arch Gen Psychiatry. · Pubmed #10632232 links to  free full text

Abstract: BACKGROUND: The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method. METHODS: Thirty-one patients with AD and 68 control subjects participated in this study. A magnetic resonance imaging method was employed that quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength magnetic resonance imaging instruments. Three basal ganglia structures (caudate, putamen, and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia ferritin iron levels were significantly increased in the caudate (P = .007; effect size, 0.69) and putamen (P = .008; effect size, 0.67) of AD subjects, with a trend toward an increase in the globus pallidus (P = .13). The increased basal ganglia ferritin iron levels were not a generalized phenomenon; white matter ferritin iron levels were unchanged in patients with AD (P = .50). CONCLUSIONS: The data replicate and extend prior results and suggest that basal ganglia ferritin iron levels are increased in AD. Prospective studies are needed to evaluate whether premorbid iron levels are increased in individuals who develop AD.