Probable Alzheimer's Disease Cases Research Articles

Findings of 18 F-PI-2620 tau PET imaging in patients with Alzheimer's disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions. 18 F-PI-2620 is one of the second-generation tau PET tracers with presumably less off-target binding than its predecessors. Although a few clinical studies have recently reported the use of 18 F-PI-2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined. In the present pilot study, we performed 18 F-PI-2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p-tau181 as well as cognitive test scores were also analyzed. The uptake of 18 F-PI-2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p-tau181 levels, as well as with MMSE and ADAS-cog scores. Our results add to accumulating evidence suggesting that 18 F-PI-2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.

The Validation of Multifactor Model of Plasma Aβ 42 and Total-Tau in Combination With MoCA for Diagnosing Probable Alzheimer Disease.

Alzheimer disease (AD) has an insidious onset and heterogeneous clinical symptoms. The well-accepted biomarkers for clinical diagnosis of AD include β-amyloid (Aβ) deposition and pathologic tau level within cerebral spinal fluid (CSF) and imaging AD pathology such as positive emission tomography (PET) imaging of the amyloid-binding agent Pittsburgh compound B (PET-PiB). However, the high expense and invasive nature of these methods highly limit their wide usage in clinic practice. Therefore, it is imperious to develop less expensive and invasive methods, and plasma biomarkers are the premium targets. In the current study, we utilized a single-blind comparison method; all the probable AD cases met the core clinical National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria and validated by PET-PiB. We used ultrasensitive immunomagnetic reduction (IMR) assays to measure plasma Aβ42 and total-tau (t-tau) levels, in combination with different variables including Aβ42 × t-tau value, Montreal Cognitive Assessment (MoCA), and Mini Mental State Examination (MMSE). We used logistic regression to analyze the effect of all these variables in the algorism. Our results showed that (1) plasma Aβ42 and t-tau are efficient biomarkers for AD diagnosis using IMR platform, whereas Aβ42 × t-tau value is more efficient for discriminating control and AD; (2) in the control group, Aβ42 level and age demonstrated strong negative correlation; Aβ42 × t-tau value and age demonstrated significant negative correlation; (3) in the AD group, t-tau level and MMSE score demonstrated strong negative correlation; (4) using the model that Aβ42, Aβ42 × t-tau, and MoCA as the variable to generate receiver operating characteristic (ROC) curve, cutoff value = 0.48, sensitivity = 0.973, specificity = 0.982, area under the curve (AUC) = 0.986, offered better categorical efficacy, sensitivity, specificity, and AUC. The multifactor model of plasma Aβ42 and t-tau in combination with MoCA can be a viable model separate health and AD subjects in clinical practice.

Borrelia burgdorferi as a risk factor for Alzheimer's dementia and mild cognitive impairment.

To determine the association of Borrelia burgdorferi infection with Alzheimer's disease or mild cognitive impairment (MCI) in older adults. Case-control study. Patients older than 60years, both sexes, were included. Three groups were created: with probable Alzheimer's disease cases with NINCDS-ADRDA criteria, MCI cases in those not meeting NINCDS-ADRDA criteria for dementia, but who had an abnormal cognitive evaluation and independence in instrumental activities of daily living (IADL), cognitively healthy controls were diagnosed with normal cognitive evaluation and independence in IADL were identified in the community. Western blot IgG against B. burgdorferi in serum was done in all the participants. Non-conditional logistic regression was applied to estimate the association of Alzheimer's disease or MCI and seropositive to B. burgdorferi. Thirty-eight patients with Alzheimer's disease, mean age of 75.6 ± 3.4years, 69% were females, education 8.3 ± 4.8years. 39 patients with MCI, mean age of 72.2 ± 6.8years, 85% were females, education 11.2 ± 4.2years. A total of 11/38 (29%) were positive to B. burgdorferi with Alzheimer's disease, 9/39 (23%) with MCI, and 11/108 (10%) of controls. In patients with Alzheimer's disease, an adjusted odds ratio (aOR) = 3.65 (95% CI 1.2-11.1) adjusted for education and a history of cerebrovascular disease (CVD) was estimated, and in patients with MCI an aOR = 3.2 (95% CI 1.1-9.1) for a history of diabetes mellitus and CVD was estimated. In our study, there was an increased risk of Alzheimer's disease and MCI in seropositive IgG patients to B. burgdorferi.

Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study.

Objective:To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD).Methods:Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47–56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999–2009). The study population included 8,195 women (227 cases of incident AD).Results:Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68–1.2, 0.99/0.75–1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31–0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome.Conclusions:Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use.

17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression.

To assess the role of rare copy number variations in Alzheimer's disease (AD), we conducted a case-control study using whole-exome sequencing data from 522 early-onset cases and 584 controls. The most recurrent rearrangement was a 17q21.31 microduplication, overlapping the CRHR1, MAPT, STH and KANSL1 genes that was found in four cases, including one de novo rearrangement, and was absent in controls. The increased MAPT gene dosage led to a 1.6-1.9-fold expression of the MAPT messenger RNA. Clinical signs, neuroimaging and cerebrospinal fluid biomarker profiles were consistent with an AD diagnosis in MAPT duplication carriers. However, amyloid positon emission tomography (PET) imaging, performed in three patients, was negative. Analysis of an additional case with neuropathological examination confirmed that the MAPT duplication causes a complex tauopathy, including prominent neurofibrillary tangle pathology in the medial temporal lobe without amyloid-β deposits. 17q21.31 duplication is the genetic basis of a novel entity marked by prominent tauopathy, leading to early-onset dementia with an AD clinical phenotype. This entity could account for a proportion of probable AD cases with negative amyloid PET imaging recently identified in large clinical series.

Recovery from Possible Late‐Onset Alzheimer's Dementia? Evidence from a Longitudinal Community‐Based Age‐Cohort Study

Recovery from Possible Late‐Onset <scp>A</scp>lzheimer's <scp>D</scp>ementia? Evidence from a <scp>L</scp>ongitudinal <scp>C</scp>ommunity‐<scp>B</scp>ased <scp>A</scp>ge‐<scp>C</scp>ohort <scp>S</scp>tudy

Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

Clinicopathologic phenotypes of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) often overlap, making discrimination difficult. We performed resting state blood oxygen level-dependent (BOLD) functional connectivity MRI (fcMRI) to determine whether there were differences between AD and DLB. Participants (n = 88) enrolled in a longitudinal study of memory and aging underwent 3-T fcMRI. Clinical diagnoses of probable DLB (n = 15) were made according to published criteria. Cognitively normal control participants (n = 38) were selected for the absence of cerebral amyloid burden as imaged with Pittsburgh compound B (PiB). Probable AD cases (n = 35) met published criteria and had appreciable amyloid deposits with PiB imaging. Functional images were collected using a gradient spin-echo sequence sensitive to BOLD contrast (T2* weighting). Correlation maps selected a seed region in the combined bilateral precuneus. Participants with DLB had a functional connectivity pattern for the precuneus seed region that was distinct from AD; both the DLB and AD groups had functional connectivity patterns that differed from the cognitively normal group. In the DLB group, we found increased connectivity between the precuneus and regions in the dorsal attention network and the putamen. In contrast, we found decreased connectivity between the precuneus and other task-negative default regions and visual cortices. There was also a reversal of connectivity in the right hippocampus. Changes in functional connectivity in DLB indicate patterns of activation that are distinct from those seen in AD and may improve discrimination of DLB from AD and cognitively normal individuals. Since patterns of connectivity differ between AD and DLB groups, measurements of BOLD functional connectivity can shed further light on neuroanatomic connections that distinguish DLB from AD.

Education, occupation and retirement age effects on the age of onset of Alzheimer's disease

To determine the effects of early life education, mid life employment and later life retirement age on the age of onset (AOO) of Alzheimer's disease (AD). Multiple regression analyses were carried out using data for 1320 probable AD cases, of which 382 were males with employment and retirement age data, using informant based information on education and employment. No relation was found between years of education, best qualification obtained, or employment variables in males and the AOO of AD. A significant effect of later retirement age in delaying the AOO of AD was seen in males. In this study no effect of education or employment was seen, although this may be due to limited variance in the study population. The significant effect of retirement age may have several explanations, the most interesting of which would be the suggestion that active employment later in life allows an individual to prolong their cognitive assets above the threshold for dementia.

Frontotemporal dementia and dementia with Lewy bodies in a case-control study of Alzheimer's disease

The clinical presentations in dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) overlap considerably with that of Alzheimer's disease (AD) despite different pathological processes. Autopsy studies have also shown that multiple brain pathology occurs frequently, even in cases with a single clinical diagnosis. We aimed to determine the frequency of clinical diagnosis of FTD and DLB and the underlying pathology in a well-characterized cohort of patients with a clinical diagnosis of probable or possible AD. We conducted a retrospective analysis of 170 AD patients (probable AD = 83; possible AD = 87) originally enrolled in a case-control study, 27 with postmortem examination, to establish the number of cases meeting probable diagnosis for FTD and DLB, using a checklist of features compiled from their consensus criteria. 23/83 probable AD cases and 32/87 possible AD cases met probable criteria for another dementia, more commonly DLB than FTD. AD pathology was present in 8/15 probable AD and 8/12 possible AD cases coming to autopsy. DLB pathology was seen in four cases and FTD pathology in eight cases. In the AD cases reaching clinical diagnosis for a second dementia syndrome and coming to autopsy, a minority showed non-AD pathology only. Presence of core clinical features of non-AD dementia syndromes is common in AD. Concordance between clinical and pathological diagnoses of dementia remains variable. We propose that repeat clinical examinations and structural neuroimaging will improve diagnostic accuracy. In addition, clinical diagnostic criteria for the main dementia syndromes require refinement.

Clinical Criteria for the Diagnosis of Alzheimer Disease: Still Good After All These Years

To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.

Incidence of Dementia, Alzheimer Disease, and Vascular Dementia in a Japanese Population: Radiation Effects Research Foundation Adult Health Study

Objective: To determine the age-, sex-, and subtype-specific incidence of dementia and to assess the effect of education level on the incidence in a Japanese population. Methods: 2,286 dementia-free subjects, aged ≧60 years, were followed for 5.9 years through biennial two-phase examinations. Results: 206 cases of dementia were newly diagnosed based on DSM IV. The incidence per 1,000 person-years was 12.0 for men and 16.6 for women. Based on NINCDS-ADRDA criteria, 80 cases of probable Alzheimer disease (AD) and 50 cases of possible AD were diagnosed. Based on NINDS-AIREN criteria, 36 cases of probable vascular dementia (VaD) and 40 cases of possible VaD were diagnosed. Age and education showed the most statistically significant effects for all dementia. Probable AD showed the most remarkable increase with age and decreased with increasing education level (p = 0.001). Probable VaD showed significant effects of sex (p = 0.033) and sex-age interaction (p = 0.048), but not education (p = 0.26). Conclusion: AD was the predominant type of dementia in this recent incidence study conducted in Japan, suggesting a reduction in VaD and an increase in AD. Age, sex, and education effects differed by dementia subtype.

Clustering and switching processes in semantic verbal fluency in the course of Alzheimer's disease subjects: Results from the PAQUID longitudinal study

Reduced semantic fluency performances have been reported in the preclinical phase of Alzheimer's disease (AD). To investigate the cognitive processes underlying this early deficit, this study analyzed the verbal production of predemented subjects for the animals category with the qualitative parameters related to clustering (i.e. the ability to generate words belonging to semantic subcategories of animals) and switching (i.e. the ability to shift from one subcategory to another) proposed by Troyer.This qualitative analysis was applied to the PAQUID (Personnes Agées QUID) cohort, a 17-year longitudinal population-based study. The performances on the animal verbal fluency task of 51 incident cases of possible and probable AD were analyzed at the onset of dementia, 2 years and 5 years before dementia onset. Each case was matched for age, sex and education to two control subjects leading to a sample of 153 subjects. The mean cluster size and the raw number of switches were compared in the two samples. The results revealed a significantly lower switching index in the future AD subjects than in the elderly controls including 5 years before dementia incidence. A significant decline in this parameter was evidenced all along the prodromal phase until the clinical diagnosis of dementia. In contrast, the mean cluster size could not discriminate the two groups. Therefore the results support the hypothesis that impaired shifting abilities – rather than semantic memory storage degradation – could explain the early decline in semantic fluency performance occurring in the predementia phase of AD.

Evidence for induction of the ornithine transcarbamylase expression in Alzheimer's disease

To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n=2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC -389 G/A and -241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.

Tumor Necrosis Factor α and Interleukin 10 Promoter Region Polymorphisms and Risk of Late-Onset Alzheimer Disease

Functional polymorphisms in tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) can affect immune response, inflammation, tissue injury, and possibly the susceptibility to Alzheimer disease (AD). To evaluate the association between promoter region polymorphisms in the TNF-alpha and IL-10 genes and risk of late-onset AD in older white subjects. Community-based case-control study. Group Health Cooperative of Puget Sound. White subjects (n = 265) meeting criteria for probable or definite AD (cases) and white control subjects (n = 347) (controls). Genotyping results for TNF-alpha, IL-10, and apolipoprotein E (APOE) genotyping. The TNF-alpha -863 A allele was associated with reduced odds of developing AD, and the test for trend suggested that having 2 copies of the A allele further reduces the risk (odds ratios [C/C, reference], 0.66 for C/A and 0.58 for A/A; P = .04). Because of linkage disequilibrium in the TNF-alpha region, we constructed promoter region haplotypes as defined by single nucleotide polymorphisms at positions -863 and -308. Based on knowledge of TNF-alpha protein production, we ordered the haplotypes based on apparent increasing transcriptional activity. After adjusting for age, education, and the presence of the APOE epsilon4 genotype, the test for trend showed increasing odds of AD with increasing transcriptional activity (P = .02). The IL-10 -1082 and IL-10 -592 allele and genotype frequencies were not significantly different between cases and controls. Variation in the TNF-alpha promoter region, or possibly polymorphisms in nearby genes, could affect cerebral inflammatory response and the risk of late-onset AD.

Peripheral cholinergic disturbances in Alzheimer's disease

The most pronounced neurochemical abnormality in Alzheimer's disease (AD) is cholinergic dysfunction in the central nervous system. Peripheral tissues may also be affected, however, including blood. The present study undertook to determine the activity of acetylcholinesterase (AChE) and its molecular forms in erythrocytes, lymphocytes and platelets of normal elderly subjects and probable AD cases. These samples contained dimeric globular (G2), tetrameric globular (G4) and asymmetric (A12) AChE forms, but no globular monomeric (G1) enzyme. In both lymphocytes and platelets, the major AChE molecular form was G2 (approximately 80%), with G4 and A12 forms accounting for nearly equal portions of the remainder. Total AChE activities and measured sedimentation coefficients were similar in the control and AD samples (from patients with mild and moderately severe cognitive deficiency). However, the groups differed significantly in the proportion of certain AChE molecular forms. Thus, as compared with controls, the amount of A12 AChE in the AD samples was increased 148 and 161% in lymphocytes and platelets, respectively. Genotyping for apolipoprotein E (ApoE) and the butyrylcholinesterase K (BCHE-K) variant, carried out using the polymerase chain reaction, showed that AD patients carried the ApoE4 allele at a significantly higher frequency than the controls. On the other hand there were no significant group differences in the occurrence of the BCHE-K variant and no synergism between ApoE alleles and the BCHE-K variant in our Hungarian AD population.

ApoE gene and familial risk of Alzheimer's disease as predictors of odour identification in older adults

The study examined odour identification ability in healthy older adults at increased risk for developing Alzheimer's disease (AD). We recruited a sample ( n = 24) of siblings related to probable AD cases and an age-matched control sample ( n = 47). All participants were genotyped for the presence of the ApoE ɛ4 allele. Performance on a simple olfactory task of odour identification was compared according to positive family history of AD and ApoE ɛ4 status. The sibling group showed an odour identification deficit compared to the control group. Whilst there was no independent influence of ApoE ɛ4 status on odour identification, there was a significant interaction between positive family history and ApoE ɛ4 status. Sibling ɛ4 carriers showed the greatest odour identification deficit and their performance was significantly poorer than both the sibling non-ɛ4 carrier and control ɛ4 carrier groups. Odour identification deficits like those reported here are considered to be early cognitive markers of incipient AD. In this respect, these findings support the need to both monitor individuals at increased risk of the disease and introduce olfactory-mediated cognitive tasks into the diagnostic setting.

No association between the cystatin C gene polymorphism and Alzheimer's disease: A case-control study in an Italian population

Cystatin C is an amyloidogenic protein found together with beta-amyloid in cerebral arteriolar walls of both patients with Alzheimer's Disease (AD) and conghopilic amyloid angiopathy. Several findings implicate cystatin C in the pathogenesis of vascular diseases. Recent genetic association studies proposed cystatin C gene (CST3) as a susceptibility factor for AD, although other reports did not replicate this finding. We conducted a case-control study including 192 probable AD cases and 192 age- and sex-matched controls to test the association between CST3 and AD. Possible interaction between CST3 and age at onset of AD or apolipoprotein E (APOE) was also examined. No significant differences in CST3 genotype or allele frequencies between cases and controls was observed, while the risk of AD increased in subjects carrying the APOE epsilon4 allele (OR 3.5, 95% CI [2.1-5.9]). There was no interaction between CST3 with age or APOE. Our findings do not support a role of CST3 gene in Italian sporadic AD.

Developmental and vascular risk factors for Alzheimer's disease

To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-ɛ4 allele was the strongest risk factor, and with increasing survival age, the effect of ɛ4 diminished. Among ɛ4 positives, developmental risk factors such as smaller head circumference (≤54.4 cm) and having more than four children in the household at age 2–3 were independently associated with incident AD (hazard ratio (HR) = 2.6 (95% CI 1.04–6.3) and 3.3 (1.2–9.2), respectively). Among ɛ4 negatives, vascular risk factors were related to AD risk (self-reported diagnoses of transient ischemic attack and diabetes (HR = 5.1, 95% CI 1.7–15.5; HR 3.3, 95% CI 1.4–8.1)). These findings indicate that clinical AD is a result of early life as well as later life risk factors, and that genetic predisposition to the disease may modify the constellation of predictors.

Apolipoprotein E −491 promoter polymorphism is an independent risk factor for Alzheimer's disease in the Chinese population

Polymorphisms at positions −491, −427 and −219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of ε2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites −491, −427, −219, and +113 in APOE gene and a polymorphic Hha1 site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for ε4 allele, only the A allele at −491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with ε4 allele, and only trends remained when cases and controls were stratified for the presence or absence of ε4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE −491 promoter alleles confer significant risk of AD independent of ε4 status.

Medication Use in Alzheimer's Disease and Healthy Aging

The purpose of this research was to determine if decreased utilization of specific medication in individuals with Alzheimer's disease (AD) reflects a global process of decreased medication usage. Participants were 1103 individuals (461 controls; 437 probable AD; 161 possible AD, and 44 Mixed Dementia), drawn from our Alzheimer's Disease Research Registry. Medication usage at entry into the registry did not differ between controls and probable AD cases. Possible AD and the mixed dementia cases took significantly more medications than controls or probable AD cases. Longitudinal analysis showed no significant changes in controls and mixed dementia cases up to 2 years, and use increased in possible and probable AD cases over time. Stratification of subjects by MMSE scores at entry showed no significant difference between groups. Medication use in probable AD patients does not differ from controls, and does not seem to be subject to systematic bias based on disease progression (as measured by MMSE scores). The presence of co-morbidity adds to medication utilization. Cognitive impairment does not appear to affect total medication use, suggesting that specific medication utilization patterns are unlikely to be the result of larger usage patterns.