Criteria For Probable Alzheimer's Disease Research Articles

Effect of Integrated Cognitive Intervention Therapy in Patients with Mild to Moderate Alzheimer's Disease.

Background and PurposeThe effect of the integrated program comprising cognitive training, art therapy, and music therapy has not been extensively studied in patients with Alzheimer's disease (AD). The present study investigated the effect of integrated cognitive intervention therapy on cognition, and activity of daily life (ADL), and mood in patients with mild to moderate AD.MethodsIn this study, the data of 59 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer disease and Related Disorders Association (NINCDS-ADRDS) criteria of probable AD among those who registered at the Centenarian's Good Memory Program in Goyang from September 2014 to August 2019 were collected. We statistically analyzed the scores of Korean version of a Mini-Mental Status Examination (K-MMSE), Korean Dementia Screening Questionnaire-Cognition (KDSQ-C), Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Seoul-Instrumental Activities of Daily Living (S-IADL) of the same patients before and after the use of integrated cognitive intervention therapy.ResultsK-MMSE slightly increased from 18.7±4.5 to 19.7±5.0 (p<0.001) and KDSQ-C improved from 14.5±7.6 before therapy to 12.6±7.2 after therapy (p=0.001). Mean S-IADL score improved from 17.6±7.6 before therapy to 15.7±9.5 after therapy (p<0.001). Additionally, mean GDS score before the therapy was 5.6±3.5 that improved to 4.2±3.0 after the therapy (p<0.001). Mean BAI score decreased from 8.4±10.3 before therapy to 5.9±8.4 after therapy (p=0.001).ConclusionsIn conclusion, this study demonstrated the possibility that the use of an integrated cognitive therapy improved cognition, ADL, and mood (depression and anxiety) in patients with mild to moderate ADs.

Intravenous immunoglobulin for Alzheimer's disease.

The foundation for using intravenous immunoglobulin (IVIg) to treat Alzheimer's disease (AD) can be traced back to the discovery, in the early 1990s, of naturally occurring anti-amyloid antibodies in human blood. A decade later, a number of independent investigators reported reduced levels of naturally occurring anti-amyloid antibodies in the spinal fluid and blood of AD patients relative to age-matched controls 1–3. Dodel subsequently reported that IVIg contained elevated levels of antibodies against amyloid-β (Aβ) monomers and proposed its use as a potential treatment for AD 4.

Does a Positive Pittsburgh Compound B Scan in a Patient With Dementia Equal Alzheimer Disease?

The clinical role of amyloid brain positron emission tomographic imaging in the diagnosis of Alzheimer disease is currently being formulated. The specificity of a positive amyloid scan is a matter of contention. An 83-year-old Canadian man presented with a 5-year history of predominantly short-term memory loss and functional impairment. Clinical evaluation revealed significant, gradually progressive short-term memory loss in the absence of any history of strokes or other neuropsychiatric symptoms. The patient met clinical criteria for probable Alzheimer disease but had a higher than expected burden of white matter disease on magnetic resonance imaging. A positron emission tomographic Pittsburgh Compound B scan was highly positive in typical Alzheimer disease distribution. The patient died of an intracerebral hemorrhage 6 months after the assessment. Autopsy revealed cerebral amyloid angiopathy in the complete absence of amyloid plaques or neurofibrillary tangles. This patient demonstrates that a positive Pittsburgh Compound B scan in a patient with clinical dementia meeting criteria for probable Alzheimer disease is not proof of an Alzheimer disease pathophysiological process. A positive Pittsburgh Compound B scan in typical Alzheimer disease distribution in a patient with dementia can be secondary to cerebral amyloid angiopathy alone.

The role of premorbid personality and cognitive factors in awareness of illness, memory, and behavioural functioning in Alzheimer's disease

Introduction. Research has suggested an association between personality factors and awareness in patients with dementia, yet valid measurement of premorbid personality is problematic. The present study aimed to better reveal the relationship between premorbid personality and awareness by using improved methodology. Moreover, the study aims to contrast the strength of the relationship of premorbid personality and awareness with that of cognitive factors. Methods. Awareness of illness, symptoms, mnemonic and behavioural impairments, and treatment compliance were measured in 27 patients with mild-to-moderate Alzheimer's disease (AD) diagnosed by standard criteria for probable AD. Participant premorbid personality was measured using average retrospective Neuroticism-Extroversion-Openness Inventory (NEO-FFI) scores from two informants. Correlations were performed to investigate the relationship between awareness and personality dimensions, as well as measures of cognitive style, neuropsychological function, mood, carer burden, and sociodemographic factors. Results. There was little relationship between awareness and personality scores, but modest associations between awareness and mood, age, and age of onset of first symptoms. Awareness of memory was related to memory functioning. Increased carer burden was associated with lack of awareness of cognitive-behavioural deficits but there were only few and weak associations between awareness and measures of cognitive functioning. Conclusions. There was little support for an association between previous personality and awareness in dementia. However, increased carer burden was associated specifically with lack of awareness of cognitive-behavioural deficits not deficits in ADL, whereas lower awareness of ADL and not cognitive-behavioural deficits was associated with age. Awareness of memory appeared to be a metamemory capacity. Mood and age rather than personality and cognition are stronger predictors of awareness in early Alzheimer's disease.

Bioavailable testosterone is associated with a reduced risk of amnestic mild cognitive impairment in older men

We investigated the risk of amnestic mild cognitive impairment (aMCI) in relation to serum bioavailable (BT) and total testosterone (TT) levels in older men. A cross-sectional study in an ambulatory setting, with older men aged 55-93 years with normal cognition, aMCI and Alzheimer's disease (AD). Morning serum BT and TT levels were determined. AD was diagnosed by the Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and aMCI by the Petersen criteria. We recruited 203 Chinese older men (48 aMCI, 66 AD and 89 with normal cognition). Mean serum BT, but not TT, levels were significantly lower in the aMCI (mean BT +/- SEM 1.06 +/- 0.10 nmol/l) and AD (0.99 +/- 0.08 nmol/l) groups than in the normal controls (1.82 +/- 0.12 nmol/l) (P < 0.001, one-way anova) with no significant difference between the aMCI and AD groups. After adjustment for education, age and apolipoprotein E (apoE) genotype, logistic regression analyses showed that the serum BT level [adjusted odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.32-0.85] was an independent protective factor for aMCI. For the combined outcome of aMCI and AD, the serum BT level was an independent protective factor but age and apoE epsilon4 were independent risk factors. There was no interaction between BT and age. In older men, serum BT, but not TT, levels were associated with a lower risk of aMCI and AD.

Validity of the Clinical Dementia Rating Scale for the Detection and Staging of Dementia in Brazilian Patients

The aim of this study was to determine the diagnostic value and agreement analyses between Clinical Dementia Rating (CDR) and dementia diagnostic criteria (gold standard), Blessed Dementia Rating scale (BDRS), and Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised (DSM III-R) criteria for severity. In a sample of 343 Southern Brazilian participants, CDR was consecutively assessed in 295 dementia patients (Alzheimer disease, vascular dementia, and questionable) and 48 healthy elderly. The National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable Alzheimer disease and the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) for probable vascular dementia were the gold standard. A battery of cognitive tests and the Mini Mental State Examination (as a screening test at study entry) were also applied. Sensitivity and specificity were obtained through contingency tables. Validity and reliability were measured through kappa coefficient, Kendall b, and percent agreement. CDR agreement among raters was demonstrated by percent agreement. Agreement to gold standard was good (kappa=0.75), as well as to the Blessed scale (kappa=0.73), and excellent to the DSM III-R (kappa=0.78). CDR detection of dementia among healthy elderly or questionable dementia was 86% and 80% sensitive, respectively, and 100% specific for both settings. In conclusion, agreement of CDR global score with the gold standard was good, and diagnostic values were high.

Vagus Nerve Stimulation in Patients With Alzheimer's Disease

Cognitive-enhancing effects of vagus nerve stimulation (VNS) have been reported during 6 months of treatment in a pilot study of patients with Alzheimer's disease (AD). Data through 1 year of VNS (collected from June 2000 to September 2003) are now reported. All patients (N = 17) met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD. Responder rates for the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Mini-Mental State Examination (MMSE) were measured as improvement or absence of decline from baseline. Global change, depressive symptoms, and quality of life were also assessed. Cerebrospinal fluid (CSF) levels for total tau, tau phosphorylated at Thr181 (phosphotau), and Abeta42 were measured by standardized enzyme-linked immunosorbent assay (ELISA). VNS was well tolerated. After 1 year, 7 (41.2%) of 17 patients and 12 (70.6%) of 17 patients improved or did not decline from baseline on the ADAS-cog and MMSE, respectively. Twelve of 17 patients were rated as having no change or some improvement from baseline on the Clinician Interview-Based Impression of Change (CIBIC+). No significant decline in mood, behavior, or quality of life occurred during 1 year of treatment. The median change in CSF tau at 1 year was a reduction of 4.8% (p = .057), with a 5.0% increase in phosphotau (p = .040; N = 14). The results of this study support long-term tolerability of VNS among patients with AD and warrant further investigation.

Differentiating Pathologic Delta From Healthy Physiologic Delta in Patients With Alzheimer Disease

In patients with Alzheimer disease, the electroencephalogram during wakefulness shows pathologic signs of abundant, diffuse, large-amplitude delta activity. The carryover of this abnormal delta activity into non-rapid eye movement sleep raises the question of whether the observed delta electroencephalographic activity during sleep in Alzheimer disease in any way reflects normal physiologic delta activity slow-wave sleep. The objective of the study was to compare patients with Alzheimer disease with age-matched controls using an experimentally controlled procedure that can test the capacity of the nervous system to generate physiologic delta-frequency responses during sleep. Research sleep laboratory. Seven ambulatory patients with Alzheimer disease (mean age = 70.0 +/- 5.77 years) meeting the National Institute of Neurological and Communicative Diseases and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease and 8 controls (mean age = 69.25 +/- 4.95 years), underwent at least 1 night of evoked-potential recordings. Data were collected during stage 2 sleep. Responses to stimuli were classified based on whether they produced a K-complex. Averages of K-complex responses were calculated, latencies and amplitudes of components evaluated, and K-complex incidence was determined. Relative to controls, subjects with Alzheimer disease produced significantly fewer evoked K-complexes (P < .001) and had substantially smaller N550 amplitudes than controls (P < .05). A lower probability of eliciting a K-complex correlated with greater dementia severity, as measured by the Mini Mental State Examination and Dementia Rating Scale. Despite observed increases in pathologic delta-frequency electroencephalographic activity, patients with Alzheimer disease have an impaired capacity to generate normal physiologic delta responses during non-rapid eye movement sleep.

Differential cognitive impairment in subjects with geriatric depression who will develop Alzheimer's disease and other dementias: a retrospective study

The aim of this study was to retrospectively differentiate the cognitive profile of subjects with geriatric depression who will later be diagnosed with Alzheimer's disease (AD) from those who will be diagnosed with other dementias, and subjects who will remain with no dementia. Forty-four depressed patients admitted to a day hospital program for depression who participated in a historical cohort study were assessed after 7.5 years of follow-up. Fourteen of these subjects subsequently developed dementia: seven met the criteria for probable AD and seven met the criteria for dementias other than AD (Dementia-No-AD; D-NAD, such as dementia with Lewy bodies (DLB), vascular and mixed dementia). Thirty subjects remained without dementia (No Dementia, ND) at follow-up. The three groups were thus compared on their baseline cognitive performances on the six sections of the Mini-mental State Examination (MMSE) and on the five subscales of the Dementia Rating Scale (DRS). An analysis of variance (ANOVA) and post-hoc Student-Newman-Keuls analyses with an alpha of p < 0.05 revealed that the subjects who received a diagnosis of dementia at follow-up had previously had more impairment on tasks measuring attention and memory (DRS-MMSE) than those who did not develop dementia (AD = D-NAD < ND). Moreover, the future AD subjects could be differentiated on the basis of their difficulties on the MMSE-orientation subtest (AD < ND = D-NAD), whereas the future D-NAD subjects initially had more problems with executive functions (DRS) and MMSE-visuospatial abilities (D-NAD < AD = ND). The identification of early neuropsychological markers in elderly depressed patients highlights the need to evaluate this population broadly as soon as possible in the depression/dementia process in order to improve the prognosis.

A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease.

Non-cognitive symptoms are a frequent feature of Alzheimer's disease (AD). Much of the literature that has accumulated pertains to cross-sectional prevalence of these symptoms. There has been relatively little attention paid to the longitudinal course of Behavioural and Psychological Symptoms of Dementia (BPSD). The purpose of this study is to examine the longitudinal course of BPSD in a group of patients with mild AD. A retrospective review of a database was performed to identify patients with NINCDS/ADRDA criteria for probable AD and who had been evaluated three times at yearly interval over a two-year period. Fifty-two subjects were identified with probable AD that had completed follow-up for 24 months. The BEHAVE-AD was used to evaluate BPSD and data was analysed using a Markov analysis. Activity disturbance is a common and relatively persistent symptom in the mild stages of AD. Anxiety, paranoid ideation, and aggression were moderately persistent. Affective symptoms were not persistent with less than half the patients having the symptoms a year later. Activity disturbance is common and persistent in early AD. Paranoid and delusional ideation shows moderate persistence and depressive symptoms infrequently last longer than a year. These findings may have clinical relevance for the pharmacological and non-pharmacological management of BPSD.

Extrapyramidal symptoms and signs in Alzheimer's disease: prevalence and correlation with the first symptom.

To determine the prevalence and clinical correlates of extrapyramidal signs (EPS) in outpatients with probable Alzheimer's disease (AD); to examine the appearance of EPS in association with the first symptom that led the patient or family to ask for medical help; to examine the association of the prevalence of EPS with gender, age at onset of the disease, duration of the disease, severity of dementia, functional disability, and potential use of neuroleptics; and to address the issue of the possible role of EPS as a predictive factor for the clinical course of the disease. We examined 126 patients meeting NINCDS-ADRDA* criteria for probable AD and 29 healthy, nondementia controls of comparable age and gender. Thirteen of the patients taking neuroleptics at the time of the examination were excluded from the main study group and formed a separate subgroup of AD/neuroleptics-positive. Twenty-eight of the AD/neuroleptics-free patients were re-examined during an 18-month period in order to determine the possible role of EPS as a predictive factor of the clinical course of the disease. Only 8 percent of the AD/neuroleptics-free patients were free of EPS, while the corresponding percentage in the control group was 61.5 percent. The most common types of EPS presented in the patient group were hypomimia ([facial mask] 60 percent), difficulty in talking (53.66 percent), bradykinesia (51.4 percent), postural instability (47.33 percent), abnormal gait (34.66), and rigidity (26 percent), respectively. No significant differences were found when examining for the presence of resting tremor, other tremors, dystonias, and dyskinesias. With regard to the presence of EPS and the first symptom, no significant difference was found among patients whose first complaint was memory disorder (probable AD) and patients with other symptoms. When examining the association between the prevalence of EPS and gender or age at onset of the disease, no special correlation was detected. However, such a correlation was found between the prevalence of EPS and duration of the disease, as indicated by the fact that EPS appear in 78.9 percent of the patients with a duration of illness less than two years, but in 97 percent of the patients with a corresponding duration of two years or more. The mean duration of the disease in patients appearing with EPS is found to be 2.68 +/- 1.98 years. The presence of EPS increases proportionally with the progression of the disease and cognitive and functional decline. Patients with poor results in the MMSE (score of less than 11) appear to present EPS at a greater percentage than those with better performance on the examination (MMSE scores greater than 11). With regard to the association between EPS and functional ability in AD, it seems that the presence of EPS imposes difficulties in daily activities, as seen by the fact that patients with EPS have lower FRSSD scores (mean +/- SD: 14.87 +/- 10.53) than patients without EPS (5 +/- 2.58). After controlling for duration of the disease, the use of neuroleptics is found to influence the appearance of EPS in patients with AD. Almost all of the patients AD/neuroleptics-positive patients presented EPS (100 percent), while 92 percent of the AD/neuroleptics-free patients manifested such symptoms. Finally, we re-evaluated 28 patients, who were part of the initial AD/neuroleptics-free group, in order to determine whether the appearance of EPS could have prognostic value for the clinical course of the disease. Patients who presented EPS at initial examination appeared to deteriorate faster, mainly cognitively, but also functionally. The mean decrease in MMSE scores in patients with EPS was found to be 2.65 +/- 3.46; while in patients without EPS at initial visit, MMSE scores were 0.63 +/- 3.88. The functional decline seems to be less influenced by the presence of EPS. The corresponding mean decrease in FRSSD scores of the two groups was 2.1 +/- 5.55 and 1.8 +/- 2.1, respectively.

Predicting Time to Nursing Home Care and Death in Individuals With Alzheimer Disease

To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. Three AD research centers. All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. (1) Requiring the equivalent of nursing home placement and (2) death. Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Demographic and clinical features of Alzheimer disease in black Americans: preliminary observations on an outpatient sample in Atlanta, Georgia.

This exploratory study describes the frequency, demographic features, and clinical manifestations of Alzheimer disease (AD) in a sample of demented black outpatients evaluated at the Emory University Alzheimer's Disease Center. The study reviews prospectively collected research data from 88 demented black outpatients who completed a standardized diagnostic evaluation. Forty-seven percent of these patients met NINCDS-ADRDA criteria for probable AD, and 29% met NINCDS-ADRDA criteria for possible AD. The majority of the probable AD patients were women, and many were suffering from comorbid medical illnesses. In the probable AD patients, there was an association between higher levels of education and a higher frequency of affective symptoms, and an association between longer duration of cognitive symptoms and the presence of parkinsonism. Possible AD was also common in this sample of demented black outpatients and was often encountered mixed with vascular dementia.

In vivo hippocampal 31P NMR metabolites in Alzheimer's disease and ageing

Memory loss is the most common early symptom of Alzheimer's disease (AD). For this study, we chose the hippocampi as regions of interest. The hippocampus, which is closely associated with memory processing, is known to be vulnerable to damage in the early stage of AD. We considered both inter-group (patients vs controls) and intra-group (right vs left hippocampus) comparisons. We examined seven patients meeting the DSM-III-R criteria of senile dementia and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS - ADRDA) criteria of probable AD, and II aged controls. This study focused on the measurement of phosphorus 31 ((31)P) Nuclear Magnetic Resonance (NMR) spectroscopy metabolites in each hippocampus. We found significant differences in phosphorus metabolites for both intra-group comparison (pH shifted towards relative alkalosis in the left hippocampus of patients) and inter-group consideration (reduced phosphodiesters [Pde]and elevated gamma adenosine triphosphate (ATP) in the right hippocampus, higher inorganic phosphate (pHi) in the left hippocampus for patients as compared to controls). We suggest energy failure and membrane functional breakdown in patients compared to aged controls.

Cerebral blood flow correlates of apathy in Alzheimer disease.

Apathy is a pervasive noncognitive neuropsychiatric disturbance in Alzheimer disease, which causes significant caregiver distress. The neuroanatomical substrate of apathy is not well understood. To study the relationship between regional cerebral blood flow and the presence and severity of the personality disturbance, apathy, in individuals with Alzheimer disease. Analysis of the relationship between regional cerebral blood flow as measured by single photon emission computed tomography and severity of apathy as measured by the Neuropsychiatric Inventory using an analysis of variance design. We examined regional cerebral perfusion alterations as measured by xenon 133Xecalibrated technetium Tc 99m hexamethyl-propyleneamine-oxime single photon emission computed tomography in relation to the presence and severity of apathy. The neurology clinics of the University of California, Los Angeles, UCLA School of Medicine, and Harbor-UCLA Medical Center. Thirty-one community-dwelling patients fulfilling National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria for probable Alzheimer disease who had a single photon computed tomographic scan performed within 3 months of administration of the Neuropsychiatric Inventory. The presence of apathy was associated with more severe prefrontal and anterior temporal dysfunction. These regional cerebral perfusion relationships with apathy were independent of cognitive decline except in the dorsolateral prefrontal cortex. These results demonstrate the association of apathetic syndromes with prefrontal and anterior temporal regional brain dysfunction and are consistent with similar findings previously reported in other disorders.

Abnormal pattern of platelet APP isoforms in Alzheimer disease and Down syndrome.

To determine if changes in levels of amyloid precursor protein (APP) isoforms in periphery are associated with Alzheimer disease and Down syndrome. After subjects were grouped according to diagnosis, APP isoform levels in platelets were compared. University medical center. Ten patients who fulfilled diagnostic criteria for probable Alzheimer disease, 22 healthy volunteers, and 7 elderly (mean age, 42.7 years) and 7 young (mean age, 19.0 years) patients with Down syndrome. The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. The ratio between the 130- and the 106- to 110-kd APP isoforms was markedly lower in patients with Alzheimer disease and in elderly patients with Down syndrome than in control subjects. In young patients with Down syndrome, the ratio did not significantly differ from that in control subjects. A consistent alteration in platelet APP isoforms has been found in Alzheimer disease and Down syndrome. Further studies will determine whether this alteration could provide a peripheral biochemical marker of the disorder and whether it could intervene in the pathogenesis of Alzheimer disease.

Hearing loss in a memory disorders clinic. A specially vulnerable population.

To determine the prevalence and characteristics of hearing loss in patients undergoing examination because of a memory disorder, to determine whether currently used screening tools were adequate for use in this specific population, and to determine if patients with Alzheimer disease reliably report hearing problems. Case-control study. A consecutive sample of 52 patients: 30 patients who met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease (group 1) and 22 patients with other forms of cognitive impairment (group 2). Patients underwent a hearing screening that included a case history, a visual inspection of the external ear canal and tympanic membrane, and pure tone audiometry. Patients and their caregivers completed a questionnaire intended to assess hearing impairment and perceived disability. Pass or fail on pure tone audiometry and pass or fail on a hearing impairment questionnaire. Of the 52 patients, 49 had significant hearing loss. No difference was found in the failure rate between patients in groups 1 and 2. In group 1, a significant discrepancy was found between the patient's self-report and that of their caregivers, whereas in group 2, the self-report was reliable. The prevalence of hearing loss in this population greatly exceeds the prevalence in healthy aged controls. The extraordinarily high prevalence of hearing loss in this selected population suggests that a hearing evaluation should be part of any assessment of cognitive function.

Memory impairment in Alzheimer's disease: replication and extension of the delayed word recall (DWR) test

AbstractObjective: The original DWR test, which measured delayed free recall, was reported to have high predictiveaccuracy in discriminating Alzheimer's disease (AD) patients from control subjects (overall accuracy of 95%).Comparison of differential performance in free recall and recognition of the same material may be of clinical interest. In the present study a delayed recognition component was added to the DWR test and the utility of both measures in discriminating AD patients from control subjects was evaluated.Procedure: This extended version of the DWR test was administered to 66 patients meeting NINCDS/ADRDA criteria for probable AD and 42 control subjects.Results: In a comparison between 42 of these patients (MMSE range 18–29), and 42 age matched healthy controls, both the delayed free recall and recognition measures were highly accurate in distinguishing patients from controls. The free recall measure achieved 98% sensitivity, specificity and overall accuracy, while the recognition measure yielded 98% sensitivity, 95% specificity, and 96% overall accuracy. The recognition performance of all 66 patients, ranging in severity from very mild to severe (MMSE range 11–29), was also evaluated to determine its relationship, if any, to measures of global cognitive impairment. While therecognition measure correlated poorly with MMSE and CAMCOG there was a modest but significant correlation with the CAMCOG memory subscale.Conclusions: In this study of highly selected AD patients both the free recall and recognition measures were sensitive and specific indicators of AD compared to control subjects. Recognition performance appears to be more closely related to degree of amnesia than to degree of global cognitive impairment.

Longitudinal changes in cognitive function and regional cerebral function in Alzheimer's disease: A SPECT blood flow study

In Alzheimer's disease (AD), SPECT imaging of regional cerebral blood flow (rCBF) has emphasized deficits in the posterior association cortex. Previous studies have shown an association between these deficits and cognitive performance, both on overall cognitive tests and more specific tests such as praxis and language. Frontal deficits have been reported in more severe patients. This has led to the conclusion that the deficit in AD, at least with functional neuroimaging, starts in the posterior association cortex, and later in the disease process “spreads” to involve the frontal cortex. This study set out to measure, in a group of AD patients, the change over time of cognitive performance and the pattern of functional deficit measured by neuroimaging. Change in function was measured using 99Tc m-HMPAO and SPECT and change in cognitive function using the CAMCOG. Two time points were used, 0 and 2 years. Twenty-four patients satisfying the DSM-III R criteria for probable AD were studied, nine of whom were subsequently diagnosed as having AD at post-mortem. The most striking finding was the effect that decreases in frontal lobe function had on cognitive function. A similar study by the same group, using the same techniques and many of the same patients but at only one time point, showed a correlation between cognitive function and rCBF in the parietal and posterior temporal lobes. This suggests that as AD patients deteriorate from unaffected to mild or moderately affected, the posterior association cortex exerts the greatest effect on cognitive deficit. In this longitudinal study, we found, using a MANOVA, that there were significant decreases over time for all the cortical regions studied, but that no region decreased significantly more than any other. In addition we found a correlation between change in frontal rCBF and change in cognitive function (both overall cognitive function and the CAMCOG sub tests of language and praxis). These data suggest, in contrast to the previous study, that as the disease progresses from mild or moderate to moderate or severe, the frontal cortex exerts the greatest effect on cognitive decline. These data support the concept of the deficit in functional imaging spreading from posterior to anterior as the disease progresses. However, both the initial pattern of deficit and the change over time were very heterogeneous when examined qualitatively. A posterior to anterior spread is the predominant pattern for the group as a whole, but individual patients, and possibly groups of patients, may well show alternative patterns.

Clinicopathologic Study of Probable Alzheimer Disease

The National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association criteria for probable Alzheimer disease (AD) require exclusion of non-AD dementia-producing conditions but do not specify how the non-AD conditions are to be identified. We addressed this issue for the case of cerebrovascular disease (CVD) by defining exclusion rules based on commonly described clinical features: (a) history of strokelike episodes; (b) history of stepwise cognitive decline; (c) focal deficits on neurological examination; and (d) evidence of significant CVD on neuroimaging. We applied these rules retrospectively to clinical records for 92 cognitively impaired patients who otherwise met criteria for probable AD and whose brains were subsequently available for postmortem examination. We used Fisher's exact test to assess the effectiveness of the exclusion rules in predicting the presence of CVD on autopsy. Prediction was better than chance when all four clinical features were used together (p = 0.0008) and when the stepwise decline or neuroimaging criteria were used alone (p = 0.03 and p = 0.05, respectively). Overall, the CVD exclusion rules were deficient because of low accuracy (50.0%) and low sensitivity (52.6%). These results support provisional use of the CVD criteria chosen for this study but suggest that modifications are needed for acceptable diagnostic accuracy and sensitivity to be achieved.