Concomitant Alzheimer Research Articles

The Lewy body, the hallucination, the atrophy and the physiology

Sir, Recent publication of Whitwell et al. (2007) in Brain offers a useful addition to our understanding of dementia with Lewy bodies (DLB). In a very large n study, they offer the most definitive evidence yet published of what previous studies have been hinting at in recent years; this being that cortical atrophy, particularly when compared to Alzheimer's disease (AD), is not a major feature of DLB. In contradistinction to a well-matched sample of AD patients, they found minimal cortical involvement in DLB and argued, very plausibly, that where atrophy was identified it could simply be a reflection of concomitant AD pathology. However, when discussing their findings with respect to visual hallucination they make the following comment: The specific structural locus of visual hallucinations is, however, unclear. Authors have suggested that deficits in the NBM (Perry and Perry, 1995; Josephs et al. , 2006), or midbrain may be critical (Manford and Andermann, 1998; Josephs et al. , 2006). Cortical regions have also been implicated (Imamura et al. , 1999; Harding et al. , 2002; Mori et …

Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline

Dementia with Lewy bodies (DLB) is a progressive dementia frequently accompanied by psychotic symptoms. Similar symptoms can occur in Alzheimer's disease (AD) to a lesser extent. The use of neuroleptic medication to treat psychosis in both diseases is of modest efficacy and can induce severe adverse reactions in DLB. Dopamine D2 receptors in the cerebral cortex are the putative target for the antipsychotic action of these drugs, but the status of these receptors in DLB is unknown. Autoradiography was used to examine the density D2 receptors in postmortem temporal cortex tissue from prospectively assessed patients with neuropathologically confirmed DLB and AD. D2 receptors were substantially (over 40%) and significantly (P < 0.001) reduced in temporal cortex in DLB, and in DLB with concomitant Alzheimer pathology, but was not significantly changed in AD. This reduction correlated with greater cognitive decline (P < 0.01), but was not significantly related to visual or auditory hallucinations or delusions. D2 receptor density was inversely correlated with cortical Lewy body pathology in the neocortex (P < 0.001). The specific loss of D2 receptors associated with Lewy body pathology, in conjunction with our previous finding of low D2 receptors in striatum in DLB, provides a possible explanation for neuroleptic intolerance. That the reduction of D2 receptors correlated with cognitive decline suggests that neuroleptics, as dopamine D2 receptor antagonists, may have a deleterious effect on cognition in DLB.

Clinical and Psychometric Distinction of Frontotemporal and Alzheimer Dementias

A proportion of patients who meet the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Associations criteria for Alzheimer disease (AD) have frontotemporal lobar degeneration (FTLD) confirmed at autopsy, with or without concomitant AD. Thus, the clinical phenotypes of the 2 disorders may overlap. To identify clinical and psychometric indicators that distinguish AD from FTLD at initial presentation. Longitudinal study of memory and aging. Alzheimer's Disease Research Center, Washington University School of Medicine. Forty-eight clinically well-characterized cases of autopsy-confirmed FTLD (27 with psychometric testing results) were compared with 27 autopsy-confirmed AD cases. Behavioral abnormalities, particularly impulsivity (P<.001), disinhibition (P<.001), social withdrawal (P = .01), and progressive nonfluent aphasia, distinguished individuals with FTLD from those with AD. The individuals with FTLD performed better than those with AD on a visual test of episodic memory (P = .01), but worse on word fluency (P = .02) (performance correlated with aphasic features). Other cognitive and clinical features, including executive dysfunction and memory impairment, were comparable between the FTLD and AD groups. Concomitant histopathological AD was present in 11 of the 48 individuals with FTLD. Clinical and cognitive features of FTLD may overlap with AD, although behavioral and language difficulties distinguish those with FTLD. Memory loss in those with FTLD may in part reflect word-finding difficulties stemming from language dysfunction. Compounding the overlap of FTLD and AD clinical phenotypes is the presence of histopathological AD in almost one fourth of individuals with FTLD.

Rivastigmine and Parkinson dementia complex

Patients suffering from Parkinson’s disease dementia (PDD) have a movement disorder, but it can be difficult to determine whether the functional impairment, which is critical in making the assessment of whether a patient has achieved the threshold for a diagnosis of dementia, is due to the dementia or the underlying Parkinson’s disease. Although the cognitive impairment found in nondemented patients with Parkinson’s disease is very dysexecutive in nature, the DSM IV (Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association IV) diagnosis of PDD has memory impairment as the defining characteristic of PDD. Severe deficits in cortical, cholinergic, excitatory, neuromodulatory input mean that memory impairment is not always due to encoding and retrieval strategy deficits, but it may also be amnesic without being related to concomitant Alzheimer’s disease pathology. Patients with PDD have a high mortality, especially when they develop hallucinations and/or are admitted to nursing homes. Of interest is the reduction in mortality that was more marked in the subgroup with visual hallucinations at baseline. The increased mortality in PD may be due to autonomic failure, evidenced by the reductions in heart rate variability in these patients. This reduction is greater in patients with hallucinations. Rivastigmine is a dual inhibitor of brain acetyl- and butyrylcholinesterases that has been evaluated in the symptomatic treatment of patients with mild-to-moderate dementia associated with idiopathic Parkinson’s disease. Although there is a need for more studies using pragmatic measures, such as time to residential care facility and both patient and carer quality of life assessments, rivastigmine appears to improve cognition and activities of daily living in patients with PDD, resulting in a clinically meaningful benefit in a large number of cases.

S1-04-04: Dementia with Lewy bodies

Dementia with Lewy Bodies (DLB) is a common cause of dementia in older people but is still associated by many clinicians with uncertainty about diagnosis and mangement . Accurate clinical diagnosis of DLB is justified by the specific functional disabilities, care needs and responses to pharmacological treatments of this group compared with other dementias. To review recent guidelines about the clinical and pathological diagnosis of DLB. The DLB International Consortium published revised methods for diagnosis and management in December 2005. No major amendments to the three core features of DLB are proposed, but better methods for measurement of symptom severity are recommended. A new category of features “suggestive” of DLB is described comprising, REM sleep behaviour disorder (RBD), severe neuroleptic sensitivity, and abnormal dopamine transporter neuro–imaging imaging. If one or more of these suggestive features is present, in addition to one or more core features, a diagnosis of probable DLB is made. Possible DLB can be diagnosed if one or more is present in a patient with dementia even in the absence of any core features. The revised criteria are also more explicit about the importance to be attached to clinical and radiological evidence of cerebrovascular disease since pathological and imaging studies suggest that white matter lesions (periventricular and deep white matter), microvascular changes and lacunes may frequently be present. For the purposes of assessing Lewy–related pathology, the latest recommendation is to use alpha–synuclein immunohistochemistry and a semi–quantitative grading of lesion density rather than the counting methods previously proposed. The pattern of regional involvement is more important than total LB count. The guidelines have also been modified to address the issue of concomitant Alzheimer type pathology to take account of the pathoplastic effect that this has upon the clinical presentation. Finally a patient management outline is offered including behavioural and pharmacological components and acknowledging that in the absence of substantial RCT evidence the recommendations are largely based upon expert opinion. New diagnostic criteria and management guidelines for DLB are now available for clinical use and further research and evaluation should be widely disemminated.

Facts, myths, and controversies in vascular dementia

Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Román, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250–260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15–20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1—Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2—Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3—Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.

The role of brain infarcts and hippocampal atrophy in subcortical ischaemic vascular dementia

We investigated if, in patients with vascular lesions, the variable that best discriminated demented from non-demented patients was the severity of the vascular pathology or the degree of hippocampal atrophy. A total of 39 patients multiple subcortical infarcts, who could be considered as possible vascular dementia with small vessel pathology, with underwent a neuropsychological study and brain magnetic resonance imaging (MRI) DSM IV criteria supported by neuropsychological data were used to distinguish demented from non-demented patients. The MRI study took into account the degree of hippocampal atrophy (hippocampal height and interuncal distance) and the severity of vascular pathology (number of brain infarcts). The distribution of lesions and a factor analysis showed that hippocampal atrophy is a better predictor of dementia than the number of brain infarcts. Multiple subcortical infarcts alone are probably not able to cause clinical dementia but the presence of vascular lesions increases the expression of concomitant Alzheimer's disease.

Forgetting in Dementia With and Without Subcortical Lacunes

Alzheimer's disease (AD) and subcortical ischemic vascular disease (SIVD) are common causes of dementia, often co-occur, and can present quite similarly, making differential diagnosis clinically challenging. This study tested the hypothesis that patients with SIVD retain information better than AD patients. Participants were 35 dementia patients with subcortical lacunes (SIVD group), 27 dementia patients without lacunar infarction (AD group), and 56 normal controls. Results indicated that despite comparable levels of initial acquisition, AD patients showed more rapid forgetting. Further analysis indicated that memory patterns within the SIVD group were heterogeneous, with some participants exhibiting rapid forgetting and some exhibiting good retention. SIVD participants with good retention showed a trend for greater executive impairments relative to SIVD participants with rapid forgetting and AD participants. Results suggest that rapid forgetting in SIVD may imply concomitant AD, whereas the dementia in patients with good retention may be purely vascular in origin. Three SIVD patients with rapid forgetting followed to autopsy all had AD pathology, further supporting the link between memory patterns and AD.

Regional distribution of alpha-synuclein pathology in unimpaired aging and Alzheimer disease.

The amygdaloid complex (AC) was found highly vulnerable to alpha-synuclein (alphaS) pathology in both familial and sporadic Alzheimer disease (AD), and recently, incidental Lewy bodies (LBs) were identified primarily in the lower brainstem. This challenges the traditional view that the substantia nigra (SN) is the region that is predominately affected in the spectrum of LB disorders. We examined the immunoreactivity of alphaS in the SN, the nucleus basalis of Meynert (nbM), and the AC in 904 subjects with or without concomitant AD pathology. AlphaS-positive structures were seen in at least one of the studied brain areas in 121 subjects (13%). The affected regions in the alphaS-positive subjects included the SN (89%), the nbM (73%), and the AC (67%). This study also included 82 sporadic AD patients diagnosed using CERAD criteria. AlphaS-positive structures were seen in 32% of the AD patients, with the SN and AC being equally affected. In a few subjects the AC was the only affected area. However, this was not inevitably associated with AD pathology, but was related to cognitive decline. Incidental LBs in the SN were described in the occasional subjects, with no alphaS pathology in the lower brainstem.

APOE E4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy.

To assess demographic and genetic determinants of Alzheimer type pathology in progressive supranuclear palsy (PSP). From a total of 173 pathologically proven cases of PSP in the Society for PSP Brain Bank, 143 patients (mean age = 74.4 years, ranging from 42 to 98 years) were suitable for genetic and pathologic study. Senile plaques (SPs) and neurofibrillary tangles (NFTs) were counted in five cortical areas, Braak stage was given, and APOE genotype was determined from DNA isolated from frozen brain tissue. The APOE allele frequency in PSP with varying degrees of concomitant Alzheimer type pathology was compared with pure PSP and autopsy controls. The relationship of APOE epsilon4 to quantitative pathologic measures was also assessed. Most patients with PSP (103 cases) had either minimal or no Alzheimer type pathology (Braak stage III or less), but 14 patients had many SPs (>20 per low power field) and a Braak stage of IV or higher consistent with pathologic criteria for AD, and 26 patients had many diffuse plaques with minimal neurofibrillary degeneration (Braak stage III or less) consistent with pathologic aging. Alzheimer type pathology was more frequent in women and older individuals with PSP, and 19 of the 40 patients with PSP with Alzheimer type pathology carried at least one APOE epsilon4 allele. The epsilon4 allele frequency was significantly higher in PSP with AD or pathologic aging than in pure PSP, and APOE epsilon4 correlated with the average maximal density of both neocortical SPs and NFTs. APOE epsilon4 is a risk factor for Alzheimer type pathology in PSP. Alzheimer type pathology is an independent process unrelated to PSP in cases with both types of pathologies.

Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank.

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

Dementias with Lewy bodies

Dementias with Lewy bodies are no rare cause of cognitive and motor impairments in old age. Neuropathologically, they must be distinguished into diffuse Lewy body disease resp. dementia with Lewy bodies, Parkinson's disease with concomitant Alzheimer's pathology, and the Lewy body variant of Alzheimer's disease according to extent and concomitant pathology. The most reliable diagnostic features of dementia with Lewy bodies are fluctuating disturbances of cognition and consciousness, visual disorders (hallucinations, visuoperceptive and visuoconstructive impairments), and early extrapyramidal signs of the hypokinetic-rigid type with a propensity to frequent falls. The pertinent diagnostic criteria are the consensus criteria according to McKeith et al. Additional contributions are to be expected by functional neuroimaging (SPECT, PET) and CSF examination (homovanillic acid). However, even assuming the most favorable conditions a diagnostic accuracy of 85 % is presently hard to achieve. Particularly, as is demonstrated using a case example, reliable antemortem diagnosis of Lewy body variant of Alzheimer's disease is hardly possible. Clinically, this group of diseases is important, since increased neuroleptic sensitivity must be taken into account and modern central cholinergic agents seem to be a promising therapeutic option.

Do risk factors for Alzheimer's disease predict dementia in Parkinson's disease? An exploratory study.

The extent to which concomitant Alzheimer's disease (AD) is etiologically related to the development of dementia in Parkinson's disease (PD) remains controversial. We explored the association of four risk factors associated with AD, including head injury, smoking, hypertension, and diabetes mellitus, with incident dementia in PD. A cohort of 180 nondemented PD patients from the Washington Heights community in northern Manhattan, New York, completed a risk factor questionnaire at baseline and was followed annually with neurological and neuropsychological evaluations. The association of baseline variables with incident dementia was analyzed by using Cox proportional hazards models. All analyses controlled for age at baseline, gender, years of education, duration of PD, and total Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline. Of 180 patients (mean age, 71.0 +/- 10.3 years), 52 (29%) became demented during a mean follow-up period of 3.6 +/- 2.2 years. Head injury risk ratio ([RR] 0.9; 95% confidence interval [CI], 0.4-2.2; P = 0.9), hypertension (RR, 0.7; 95% CI, 0.4-1.4, P = 0.3), and diabetes mellitus (RR, 0.8; 95% CI, 0.3-2.3; P = 0.7) were not significantly associated with incident dementia in the Cox models. Patients who reported having ever smoked were at increased risk for the development of dementia compared with nonsmokers (RR, 2.0; 95% CI, 1.0-3.9; P = 0.05). Current smoking was significantly associated with incident dementia (RR, 4.5; 95% CI, 1.2-16.4; P = 0.02), whereas past smoking approached significance (RR, 1.9; 95% CI, 0.9-3.7; P = 0.07). Although an inverse association between smoking and PD has been reported in several studies, our study showed a positive association between smoking and dementia in the setting of PD. The association of smoking with incident dementia in PD deserves further study.

Alpha-synuclein pathology is highly dependent on the case selection.

Lewy bodies and dystrophic neurites have been considered a common substrate for dementia, but they are also frequently found in the normal elderly population. The primary component of this pathology involves alpha-synuclein. The main objective of the present study was to estimate the prevalence of alpha-synuclein pathology in aged population, and to assess its relative significance in relation to dementia. The study also investigated whether differences could be detected in alpha-synuclein pathology in relation to age, gender or concomitant Alzheimer's pathology. Furthermore, the influence of sampling strategies was analysed. Alpha-synuclein pathology was assessed using immunohistochemistry in well-characterized post-mortem material. The investigation included patients from a longitudinal study of dementia of Alzheimer's type (n = 103, 85% demented), subjects from a prospective longitudinal clinical study of ageing (n = 69, 29% demented), a cohort of consecutive clinical post-mortem cases collected for 1 year (n = 262, 12% demented), a sample of forensic post-mortem cases collected for 6 months (n = 121, 15% demented) and a sample of Brain Bank material (n = 234, 26% demented). Overall, alpha-synuclein pathology was found in 14% of all 774 subjects over 40 years of age, and this percentage varied from 8% to 27% according to sampling strategies. These results indicate that the prevalence of alpha-synuclein pathology clearly depends on the selection of material. Furthermore alpha-synuclein pathology was found in 23% of clinically demented patients and in 11% of non-demented subjects. The load of alpha-synuclein pathology was significantly greater in the demented patients versus non-demented subjects indicating that alpha-synuclein pathology is indeed of importance in the pathogenesis of dementia.

Frontal lobe hypometabolism predicts cognitive decline in patients with lacunar infarcts.

A proportion of patients with subcortical lacunes will suffer progressive cognitive dysfunction, but the basis for this decline is controversial and little is known about predicting cognitive decline in these patients. Studies of Alzheimer disease have shown that imaging measures of temporal and parietal metabolism and blood flow predict disease course. To determine whether regional cerebral glucose metabolism predicts cognitive decline by testing 2 opposing hypotheses: (1) temporoparietal activity predicts decline (based on the idea that concomitant Alzheimer disease causes decline) vs (2) frontal hypometabolism predicts decline (based on evidence that subcortical frontal circuits are especially vulnerable to small vessel ischemia). Prospective cohort study. University outpatient dementia center. A convenience sample of 26 patients with radiologically defined lacunes and baseline cognitive function ranging from normal to moderately demented. Regional cerebral metabolism was quantitated in the form of atrophy-corrected positron emission tomographic activity ratios in cortical regions that were defined a priori. Patients were followed up at a mean of 1.8 years, and the dependent variable was rate of change in the Mini-Mental State Examination score. Bilateral and right hemisphere dorsolateral frontal metabolism significantly predicted cognitive decline, with right dorsolateral frontal metabolism explaining 19% of the variance. No other positron emission tomographic region was a significant predictor, nor were demographic variables or baseline Mini-Mental State Examination scores significant predictors. Cognitive decline in patients with lacunes may result in part from progressive vascular compromise in subcortical frontal circuits.

Auditory event-related potentials differentiate patients with normal pressure hydrocephalus and patients with concomitant Alzheimer's disease verified by brain biopsy.

We studied 51 patients with clinical symptoms and CT findings suggesting normal pressure hydrocephalus (NPH). Tests included head MRI, auditory event-related potentials (ERPs), thorough neuropsychological testing and intraventricular intracranial 24 h pressure recording and infusion testing. A brain biopsy was also obtained to verify a concomitant dementing process (Alzheimer's disease; AD). Patients were divided into subgroups according to the need of shunt and the biopsy findings, and their ERPs were analysed blindly. The present results suggest that non-invasive ERPs aid in the differentiation of pure NPH from NPH with concomitant AD.

Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) gene interactions with the apolipoprotein E ε4 allele as risk factors in Alzheimer's disease and in Parkinson's disease with coexisting Alzheimer pathology

Alzheimer's disease (AD) and Parkinson's disease (PD) are genetically heterogeneous. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) genes may modify the risk of these disorders. We investigated whether common polymorphisms...

Apolipoprotein E genotype and cerebral amyloid angiopathy-related hemorrhage.

Following the identification of the role of the apolipoprotein E (APOE) gene polymorphism in Alzheimer's disease (AD), this gene was examined in cerebral amyloid angiopathy (CAA). As in AD, the APOE epsilon 4 allele was found to be associated with CAA. Lobar intracerebral hemorrhage is the major clinical manifestation of CAA. Initial studies on a small number of patients with CAA-related hemorrhage (CAAH) identified overrepresentation of APOE epsilon 4. However, it became clear that confounding bias from concomitant AD and the need for pathologically confirmed cases of CAAH would also have to be considered. A larger series of pathologically confirmed cases of CAAH, also assessed for AD pathology, found a surprising overrepresentation of the APOE epsilon 2 allele. Because of the association between CAA and AD, it might have been predicted that patients with CAAH would have a low, rather than a high, epsilon 2 frequency. The overrepresentation of APOE epsilon 2 was present both in patients with and without AD, whereas a high epsilon 4 frequency correlated with concomitant AD. Further studies found that overrepresentation of APOE epsilon 2 is specific for CAAH and is not found in intracranial hemorrhages due to other causes. In CAAH, APOE epsilon 2 may interact with putative risk factors for hemorrhage, including antiplatelet/anticoagulant medication, minor head trauma, and hypertension. Several microvascular abnormalities in amyloid-laden blood vessels have been assumed to antedate CAAH and increase its likelihood. APOE epsilon 2 has now been found to be associated with some of these vascular abnormalities, specifically a "double-barrel" appearance and fibrinoid necrosis. The currently favored interpretation is that APOE epsilon 4 enhances deposition of amyloid-beta protein in the walls of cerebral blood vessels, whereas epsilon 2 is a risk factor for hemorrhage from amyloid-laden blood vessels by promoting specific "CAA-associated vasculopathies."

Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease.

We studied the plasma chain-breaking antioxidants alpha carotene, beta carotene, lycopene, Vitamin A, Vitamin C, Vitamin E and a measure of total antioxidant capacity, TAC, in 79 patients with Alzheimer's disease (AD), 37 patients with vascular dementia (VaD), 18 patients with Parkinson's disease and dementia (PDem), and 58 matching controls, together with 41 patients with Parkinson's disease (PD) and 41 matching controls. Significant reductions in individual antioxidants were observed in all dementia groups. When compared to controls, the following were reduced: Vitamin A in AD (p < 0.01) and VaD (p < 0.001); Vitamin C in AD (p < 0.001), VaD (p < 0.001) and PDem (p < 0.01); Vitamin E in AD (p < 0.01) and VaD (p < 0.001); beta carotene in VaD (p = 0.01); lycopene in PDem (p < 0.001). Lycopene was also reduced in PDem compared to AD (p < 0.001) and VaD (p < 0.001). Antioxidant levels in PD were not depleted. No significant change in TAC was seen in any group. The reduction in plasma chain-breaking antioxidants in patients with dementia may reflect an increased free-radical activity, and a common role in cognitive impairment in these conditions. Increased free-radical activity in VaD and PDem could be associated with concomitant AD pathology. Individual antioxidant changes are not reflected in TAC.

Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer’s disease: a community based follow up study

OBJECTIVESBiochemical markers for Alzheimer’s disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau)...