Neurological And Communicative Disorders And Stroke-Alzheimer's Disease And Related Disorders Association Research Articles

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans

We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

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.

The prevalence of sarcopenia and dynapenia according to stage among Alzheimer-type dementia patients.

In this study, the aim was to identify the prevalence of sarcopenia and dynapenia according to disease stage among Alzheimer-type dementia (AD) patients and collect data to suggest precautions related to reducing the disease load. The study was completed with 127 patients separated into stages according to Clinical Dementia Rating Scale (CDR) criteria and 279 healthy volunteers aged 18-39 years and 70-80 years abiding by the exclusion criteria who agreed to participate in the research. Our prospective and cross-sectional study applied the CDR and mini mental test (MMSE) to patients with disorder in more than one cognitive area and possible AD diagnosis according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) diagnostic criteria. The patient and control groups had skeletal muscle mass index (SMMI), muscle strength and physical performance assessed with sarcopenia diagnosis according to European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria. In our study, in parallel with the increase in disease stage of AD patients, the prevalence of sarcopenia (led by severe sarcopenia) and dynapenia was higher compared to a control group of similar age. In chronic, progressive diseases, like AD, identification of changes in parameters, like muscle mass and strength and reductions in physical performance in the early period, is important for identification and to take precautions in the initial stages considering the limitations of the preventive effects of treatment applied after diagnosis of AD.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

IntroductionThis study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a...

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

Incidence of Alzheimer′s disease in India: A 10 years follow-up study

To determine overall and age-specific incidence rates of Alzheimer's disease (AD) in a southern Indian province, Kerala. A 10-year (2001-2011) prospective epidemiologic study of community residing subjects aged ≥55 years at enrollment. The catchment area included four urban and semi-urban regions of Trivandrum city in Kerala, India, was selected to provide a range of demographic and socioeconomic representation. Cognitive and functional ability screening were done at baseline and 24-month follow-up assessments. Consensus diagnostic procedures were done using the Diagnostic and Statistical Manual of Mental Disorders, 4 th edition (DSM-IV), and the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for the diagnosis of dementia and AD. Among the 1066 eligible participants who were cognitively normal at baseline, 104 developed dementia (98 with AD) over a follow-up period of 8.1 years. The incidence rates per 1000 person-years for AD was 11.67 (95% CI: 10.9-12.4) for those aged ≥55 years and higher for those aged ≥65 years (15.54, 95% CI: 14.6-16.5). In those aged ≥65 years, the world age standardized incidence rate was 21.61 per 100,000, and standardized against the age distribution for the year 2000 U.S. Census, the age-adjusted incidence rate was 9.19 (95% CI: 9.03-9.35) per 1000 person-years. Incidence rate of AD increased significantly and proportionately with increasing age. These are the first AD incidence rates to be reported from southern India. The incidence rates appear to be much higher than that reported from rural north India, comparable with that reported from China, and marginally lower than that reported from the western world.

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.

Effects of donepezil on Alzheimer's disease: The relationship between cognitive function and rapid eye movement sleep

The aim of this study was to observe the effects of donepezil on both the cognitive function and sleep patterns in patients of Alzheimer's Type Dementia (ATD), especially to determine the relationship between the improvement of cognitive function and the amount of rapid eye movement (REM) sleep. A total of 12 patients (7 females, 5 males; age, 73.0 +/- 6.8) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria of probable AD were studied. These patients presented with mild to moderate dementia, which was confirmed by a Clinical Dementia Rating score of 1 or 2. Following baseline examinations consisting of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog) and polysomnography (PSG), 5 mg of donepezil was administered to the patients at breakfast every day. All patients were reassessed 6 weeks later using the same examinations. With sleep patterns, the percentage of REM sleep to total sleep time increased after the administration of donepezil. In addition, it was also found that sleep efficiency was increased and sleep latency was shortened by this administration. Although the ADAS-Jcog score did not decrease significantly, there was significant positive correlation between the decrease of the ADAS-Jcog score and the increase in the percentage of REM sleep. These results indicate the increase action of REM sleep due to activate central cholinergic systems and the possibility to improve sleep conditions due to one-time administration after breakfast of donepezil in mild to moderate ATD. It is concluded that the increase in REM sleep may reflect the improvement of cognitive function in ATD patients.

Correlates of delayed referral for the diagnosis of dementia in an outpatient population.

Early diagnosis of dementia is critical, but there is usually a time lag between onset of symptoms and referral for neuropsychological testing and dementia diagnosis. We aimed to identify factors correlated with this delayed referral. We studied 140 patients with cognitive deterioration referred to the Memory Clinic of the Catholic University (Rome) between 1995 and 1996. Alzheimer's disease or multi-infarct dementia was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and Hachinski ischemic score. Global cognitive and neuropsychological functions were assessed with the Mini-Mental State Exam (MMSE) and the Mental Deterioration Battery. The performance on the Activities of Daily Living was used to measure physical function. The time between onset of signs of cognitive deterioration and referral for diagnosis (time to diagnosis: TTD) was estimated through a semistructured interview of the caregiver. Independent correlates of TTD were identified after adjustment for potential confounders and stratifying patients based on level of physical function. Of 127 eligible patients, 63% had Alzheimer's disease, 26% multi-infarct dementia, and 11% had dementia of other types. Mean age was 73.9 +/- 8.2 years, and 59% of patients were females. The mean TTD was 13.8 +/- 10.8 months and did not differ by gender, household composition, or type of dementia. For patients with normal physical function, increased age (beta = .50), female sex (beta = .51), and low MMSE score (beta = .36) were associated with longer TTD. Among patients with physical impairment, only MMSE score showed an association with TTD, but it was of opposite direction (beta = -.31). These associations were consistent by type of dementia. Age, gender, and degree of cognitive impairment are important correlates of the time between onset of signs/symptoms and referral for dementia diagnosis. These factors are independent of the type of dementia but are influenced by the level of physical function.

Carga y calidad de vida en cuidadores de pacientes con demencia tipo Alzheimer

To analyze the factors which affect the burden and quality of life in carers of patients with Alzheimer's disease. From a sample of 234 carers of patients in the Unit for Assessment of Memory and Dementia with a diagnosis of probable Alzheimer's disease, according to the scale of National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA), and of minimal or slight severity, according to the Cambridge Mental Disorders of the Elderly Examination (CAMDEX) criteria, we obtained sociodemographic variables and administered the following questionnaires: Neuropsychiatric Inventory (NPI), Rapid Disability Rating Scale (RDRS-2), Quality of Life Questionnaire (QLQ) and Burden Interview (BI). The sex of the carers, the hours of attention to the basic activities of daily life (BADL) and the Cambridge Cognitive Examination (CAMCOQ), Minimental State Examination (MMSE), QLQ, NPI and RDRS-2 scores were related to the BI score. Multiple regression accepted the scoring for NPI, RDRS-2 and QLQ in the model. The QLQ score was associated with male sex of the patient, the age of the carer, employment status, whether or not he lived with the patient, with the family relationship, the hours of attention to the BADL and the scores on CAMCOG, MMSE, RDRS-2, NPI and BI. The multiple regression model included the age of the carer, the BI score and the hours of attention to the BADL. The non-cognitive symptoms, functional disability and poor perception of quality of life are factors affecting the burden and age of the carer, the hours of attention to the BADL and the burden affecting quality of life.

Discriminant Analysis of Brain Imaging Data Identifies Subjects With Early Alzheimer's Disease

In vivo functional brain imaging provides an opportunity to quantify and localize functional deficits associated with Alzheimer's disease (AD), in relation to dementia severity and heterogeneous cognitive profiles. Such imaging also provides a basis for distinguishing AD from other causes of dementia and for making an early diagnosis of disease. One imaging modality that can elucidate AD is positron emission tomography (PET), which is used to measure regional cerebral metabolic rates for glucose (rCMRglc) and regional cerebral blood flow (rCBF). Resting-state measurements with PET, when related to cognitive profiles in longitudinal studies, indicate that specific cognitive defects are preceded and predicted by reductions in rCMRglc in regions subserving the cognitive functions tested. Metabolic reductions and right/left metabolic asymmetries can be used to convert a "possible" to a "probable" diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. Furthermore, discriminant analyses of PET metabolic patterns can identify patients at risk for AD with mild memory deficits as having probable AD. In the future, stimulation PET studies should augment the power of this discriminant analysis.

Clinical assessment of Alzheimer's disease.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was established in 1986 to develop standardized methods to evaluate persons with Alzheimer's disease (AD) and gather clinical, neuropsychological, and neuropathologic information about this illness. CERAD clinical battery. The clinical assessment protocol(table 1) was designed to provide clinicians with the minimum information necessary to make a confident diagnosis of AD.1 The battery includes reliable and validated measures or those of time-honored value. Information is obtained through semistructured interviews with the patient and an informant, a general physical and neurologic examination of the patient, and brief cognitive scales. Questions are asked regarding prior illnesses and injuries and symptoms of depression. Other questions cover the history of possible symptoms of dementia, medications that might contribute to such symptoms, and duration of the dementing process. We administer a modified Blessed Rating Scale for Dementia2 to determine informant-reported changes in instrumental and basic activities of daily living and the Short Blessed Test3 to measure orientation, memory, and concentration. We evaluate the patient's language, calculation, and visuospatial performance. Laboratory studies include a routine hemogram and biochemical screen, thyroid function test, and vitamin B-12 level. Neuroimaging of the brain by either CT or MRI is required. A protocol for obtaining and reading neuroimages has been developed.4 Global severity of dementia is staged in accordance with the Clinical Dementia Rating (CDR) scale.5(With evaluation of the cases until death, the stages assessed by the CDR have been validated and expanded to include profound [coded as 4] and terminal[coded as 5].)6 Diagnostic criteria for AD are those proposed by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association(NINCDS/ADRDA)7 modified to require memory loss of at least 12 months' duration (instead of 6 months), and …

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.

Clinical-Neuropathological Correlations in Alzheimer's Disease and Related Dementias

To compare neurologists' initial clinical diagnoses made according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition guidelines with neuropathological diagnoses of Alzheimer's disease (AD) and related dementias. Consecutive autopsies in a prospective cohort study. Community-dwelling patients with dementia referred to neurologists at an Alzheimer's Disease Research Center and satellite clinics (n = 151) and patients initially evaluated when institutionalized (n = 19). Of 204 elderly patients who had an autopsy performed, 170 had received a complete dementia evaluation according to NINCDS-ADRDA guidelines. Percentage agreement between neurologists' initial clinical diagnoses and pathological findings. Of 137 patients clinically diagnosed as having probable or possible AD, 123 (90%) had AD neuropathological findings; this included 29 with AD accompanied by Lewy bodies, and 14 with AD and one or more infarcts. Cases of vascular and mixed dementia (AD and infarct[s]) had lower rates of agreement with pathological findings. Possible AD cases were more likely than probable AD cases to show pathological features other than AD. Clinicians predicted the presence or absence of AD pathological findings significantly better than chance. In patients with AD pathological lesions, older age of onset and male gender were significantly associated with shorter duration from disease onset to death. Clinicians accurately predicted AD pathological findings or their absence in most cases. Attributing other degenerative dementias to AD, misdiagnosing patients with combined AD and Lewy bodies and misjudging the vascular contribution to dementia were the major areas of inaccuracy. Formal criteria for dementia associated with non-AD lesions, Lewy bodies, and infarcts need to be developed and tested.

Alzheimer's disease: the problem of incorrect clinical diagnosis.

We reviewed the medical records of eight patients clinically diagnosed with Alzheimer's disease who were found on autopsy to have neuropathologic findings inconsistent with Alzheimer's disease. The clinical criteria for the diagnosis of probable Alzheimer's disease from the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) were retrospectively applied to these patients. The patients presented with clinical features atypical for Alzheimer's disease early in the course of the disease, including focal neurologic findings, gait abnormalities, motor speech abnormalities, and extrapyramidal features. Attention to these clinical red flags may decrease the likelihood of misdiagnosis of Alzheimer's disease in a patient with a non-Alzheimer's disease cause of dementia.