Comparison of reading and spelling in patients with probable Alzheimer's disease.

Patients with probable Alzheimer's disease (AD) are reported to show mild, but reliable, difficulties reading aloud and spelling to dictation exception words, which have unusual or unpredictable correspondence between their spelling and pronunciation (e.g., touch). To understand the cognitive dysfunction responsible for these impairments, 21 patients and 27 age- and education-matched controls completed specially designed tests of single-word oral reading and spelling to dictation. AD patients performed slightly below controls on all tasks and showed mildly exaggerated regularity effects (i.e., the difference in response accuracy between words with regular spellings minus exception words) in reading and spelling. Qualitative analyses, however, did not demonstrate response patterns consistent with impairment in central lexical orthographic processing. The authors conclude that the mild alexia and agraphia in AD reflect semantic deficits and nonlinguistic impairments rather than a specific disturbance in lexical orthographic processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monitoring frequency of occurrence without awareness: evidence from patients with Alzheimer''s disease

Mouse mammary tumor virus (MMTV) is a type B retrovirus that is transmitted as an infectious milk-borne particle and that causes mammary carcinomas by insertional activation of cellular protooncogenes. Germ line infections result in endogenous Mtv proviruses integrated in the genome of most mouse strains. These endogenous proviruses have been integrated into the genomes of mice for only the past 3-5 million years. The open reading frame present in the 3' long terminal repeat (LTR) of the provirus encodes a superantigen (SAg) which is able to stimulate a large proportion of T cells sharing a common T-cell receptor beta chain variable domain (v beta). Expression of this SAg is critical to the MMTV life cycle. After expression of the SAg in B cells a significant number of T cells are recruited to respond to these MMTV infected cells. As a consequence both the T cells expressing the relevant TCR V beta domain and the infected B cells become activated and start dividing. This would facilitate integration of MMTV and amplify the number of virus infected lymphocytes. Most likely during lactation the mammary glands become receptive to viral infection. The presence of endogenous Mtvs induces an early clonal deletion of reactive T cells. For this reason it has been argued that the presence of these proviruses confers a selective advantage to the mouse population by protecting the host from infection with an exogenous MMTV coding for a cross-reactive SAg. However, recent results discussed herein suggest that Mtv proviruses may also be detrimental to the mouse population by participating in recombinations with exogenous MMTVs, giving rise to highly tumorigenic recombinant particles. These results are discussed in the light of recent reports suggesting the involvement of viral sequences with a high homology to MMTV in human mammary tumorigenesis.     

Deterioration of generic knowledge in patients with Alzheimer's disease: evidence from the Number Information Test

Semantic memory for generic knowledge was assessed in patients with probable Alzheimer's disease (AD; n = 142) and elderly normal control (NC; n = 78) subjects using the Number Information Test (NIT), a test that consists of 24 general knowledge questions that require a single number for an answer (e.g., "How many days are in a year?"). The results showed that patients with AD were impaired, even in the mildest stage of dementia, and that this impairment grew as the severity of their dementia increased over time. In addition, patients with AD were highly consistent in the individual items they missed in subsequent test sessions conducted 1 or 2 years later. These results indicate that semantic memory for generic knowledge is impaired relatively early in AD, deteriorates throughout the course of the disease, and may be due to a loss of knowledge rather than to a retrieval deficit.     

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.     

Reading of lexically stressed words by Italian aphasic patients: A retrospective study.

This retrospective study investigated whether there is evidence of a 3rd reading mechanism in a transparent orthography such as Italian, where (nearly) all words can be read through the sublexical route but stress cannot always be assigned by orthography-to-phonology rules. The presence and frequency of stress errors in lexically stressed words in 16 aphasic patients with impaired reading comprehension of those same words was checked. Nine patients were reexamined months later. Notwithstanding impaired reading comprehension, none of the patients made stress errors at first examination. At follow-up, all patients showed improvement of reading comprehension and only 2 patients still had better preserved oral reading. The authors concluded that even in transparent orthographies such as Italian, the noninteractive dual-route model is inadequate for explaining all patterns of reading performances. In nonprogressive aphasias, reading comprehension can recover in a large number of patients, reducing the amplitude of the dissociation between reading aloud and reading comprehension and reducing the number of patients showing this dissociation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Early probable Alzheimer's disease and awareness context theory

The purpose of this research was to explore the explanatory value of Awareness Context Theory for social interactional issues in early probable Alzheimer's Disease (AD). Glaser and Strauss's Awareness Context Theory [Glaser and Strauss (1965) Awareness of Dying, Aldine, New York] served as the framework for the analysis of interview data from 14 early probable AD clients and 14 family caregivers, a written autobiographical account, a fictionalized account, observations of a family care-giver focus group, and excerpts that focused on early AD from field notes recorded during two years of participant observation at a specialized AD daycare center and a family caregiver support group. Initial open-ended study questions focused on the experience of early AD from the diverse perspectives represented in the data. After preliminary analysis of data suggesting emergent fit with Awareness Context Theory, questions were refocused to address awareness contexts. Data were coded and analyzed for fit with the theory. Awareness Context Theory provided a useful heuristic for thinking about the nuances and complexities of social interaction in early AD. Attention to awareness contexts should enable health care providers to suggest interventions to improve caregiver-client interactions.     

Neurological disorders in dentistry: managing patients with Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent type of dementing illness affecting over four million Americans. It typically occurs after age 60, and prevalence increases with advanced age. As the adult population increases, a greater number of patients with a diagnosis of AD will require dental care. This article reviews the oral and systemic clinical findings seen in AD patients and current medical treatment. Some general and specific suggestions for dental management are presented, including guidelines for restraint and sedation use. Finally, some helpful, adaptive oral devices are recommended for use by caregivers of patients unable to provide for their own daily oral hygiene. Dental providers can and should be willing to make oral care available to patients with a diagnosis of AD. Despite the difficulties involved, the need will continue to be great, and the gratification in caring for these patients makes it worth the effort.     

Psychiatric correlates of MR deep white matter lesions in probable Alzheimer's disease

The authors examined the relationship between psychiatric symptoms and the presence of of MR deep white matter lesions (DWMLs) in 28 probable Alzheimer's disease (AD) patients with mild to moderate dementia. The difference in frequency of psychiatric symptoms between patients with and without DWMLs was not statistically significant. However, MR global scores of severity correlated with the presence of ideational disturbances (such as low self-esteem and suicidal ideation). Analysis of specific cerebral regions indicated that the highest correlation occurred in the frontal white matter. Thus, DWMLs are correlated with specific symptoms of depression in AD. Whether DWMLs are etiologically related to these symptoms remains to be determined.     

No evidence for a higher resting metabolic rate in noninstitutionalized Alzheimer's disease patients

OBJECTIVE: It has previously been suggested that Alzheimer's disease patients have higher resting energy requirements than healthy individuals, which may contribute to their unexplained weight loss. We examined whether resting metabolic rate, the largest component of daily energy expenditure, is elevated in Alzheimer's patients compared with healthy older controls. DESIGN: Cross-sectional. SETTING: General Clinical Research Center and Baltimore VA Medical Center. PATIENTS: Twenty-five noninstitutionalized demented patients (74 +/- 8 years; mean +/- SD) with a wide range of Mini-Mental Examination scores (1 to 20) and 73 healthy older individuals (69 +/- 7 years). MEASUREMENTS: Resting metabolic rate was measured by indirect calorimetry, fat-free mass and fat mass by dual energy X-ray absorptiometry, and daily energy intake by food diaries. RESULTS: No differences in fat-free mass and fat mass were noted between Alzheimer's disease patients and healthy older controls. Resting metabolic rate was similar in Alzheimer's disease patients (5446 +/- 962 kJ/day) and healthy older individuals (5647 +/- 887 kJ/day). These results persisted when resting metabolic rate was statistically adjusted for differences in body composition and age. CONCLUSION: These results provide no evidence for an elevation in resting energy requirements in noninstitutionalized demented patients.     

Classical conditioning in patients with Alzheimer's disease: A multiday study.

Previous studies demonstrated that patients with Alzheimer's disease (AD) do not acquire the classically conditioned eyeblink response. These studies, however, were only tested over a single conditioning session and, hence, raise the question of whether AD patients are capable of acquiring the response if sufficient training is given. This question may be of some importance because whether AD patients can ultimately acquire the response has implications for the underlying neurobiological deficit in disrupted conditioning in AD. This study tested AD patients and age-matched controls over 4 days. As in previous studies, AD patients performed significantly worse than controls on Day 1, but by Day 4, they were not significantly different from controls. Subsequent testing indicated that these effects were not due to nonassociative variables such as changes in sensitivity to stimuli or disruption of the motor response. Also, it was reported that neither AD patients nor controls showed any evidence of acquisition in an explicitly unpaired paradigm, suggesting that neither pseudoconditioning nor sensitization is contributory. Data are discussed in terms of the possible role of the hippocampus in mediating conditioning deficits in AD patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations in glucose metabolism in patients with Alzheimer's disease

OBJECTIVE: To determine the alterations in glucose metabolism that occur in patients with Alzheimer's Disease (AD). DESIGN: Cross-sectional comparison of AD and healthy controls. SETTING: A University teaching hospital. PATIENTS: Healthy controls (n = 14, BMI: 24.9 +/- 0.5 kg/M2, age 73 +/- 1 years) and patients with AD (n = 12, BMI: 23.9 +/- 1.0 kg/M2, age 72 +/- 1 years). All controls and patients with AD had a normal history and physical examination, a negative family history of diabetes, and took no medications. MEASUREMENTS: All patients and controls underwent an assessment of their dietary intake and physical activity, a 3-hour oral glucose tolerance test (OGTT), and a 2-hour hyperglycemic glucose clamp study. RESULTS: Total caloric intake (AD: 27.1 +/- 1.3 kcal/kg/day; Control: 23.6 +/- 1.6 kcal/kg/day; P = ns) and intake of complex carbohydrates (AD: 5.9 +/- 0.4 kcal/kg/day; Control: 6.5 +/- 0.3 kcal/kg/day; P = ns) were not different between groups. Leisure time physical activity was greater in controls (AD: 2970 +/- 411 kcal/week; Control: 5229 +/- 864 kcal/week; P < 0.05). Patients with AD had higher fasting glucose (AD: 5.9 +/- 0.2 mmol/L; Control: 5.1 +/- 0.1 mmol/L; P < 0.01) and insulin (AD: 144 +/- 20 pmol/L; Control: 100 +/- 6 pmol/L; P < 0.05) values. In response to the OGTT, the area under the curve for glucose and insulin was similar in both groups. During the hyperglycemic clamp, steady-state glucose values were higher in the Alzheimer's patients (AD: 11.5 +/- 0.2 mmol/L; Control: 10.9 +/- 0.1 mmol/L, P < 0.01). First- and second-phase insulin responses were similar in each group. The insulin sensitivity index (units: mL/kg.min per pmol/L x 100), a measure of tissue sensitivity to insulin, was reduced in the patients with AD (AD: 0.59 +/- 0.06; Control: 0.79 +/- 0.07; P < 0.05). CONCLUSIONS: We conclude that early AD is characterized by alterations in peripheral glucose metabolism, which may relate, in part, to alterations in physical activity.     

Providing dental care for patients diagnosed with Alzheimer's disease

Alzheimer's disease is the most common dementing illness affecting over 4 million Americans. As the population ages, dentists and other health care providers will be faced with the daunting task of managing an increasing number of people with this disease. Currently, there are no definitive medications to treat this disease, although there are a number of recent drugs which may help to alleviate some symptoms. This article reviews the current medical treatment and the dental concerns which face the dentist, patient, and family. Suggestions for dental management are given along with practical recommendations for caregivers.     

Signal transduction abnormalities in Alzheimer's disease: evidence of a pathogenic stimuli

Hippocampal and select cortical neuronal populations in Alzheimer's disease exhibit phenotypic changes characteristic of cells re-entering the cell division cycle. Therefore, in this study, we investigated whether components, known to trigger cellular proliferation and differentiation, upstream of the ras/mitogen-activated kinase pathway, could contribute to the activation of a signal transduction cascade in Alzheimer's disease. We found that proteins implicated in signal transduction from cell surface receptors via the ras pathway, namely Grb2 and SOS-1, were altered in cases of Alzheimer's disease in comparison to age-matched controls. SOS is increased in susceptible pyramidal neurons, while Grb2 shows more subtle alterations in subcellular distribution. Importantly, both SOS-1 and Grb2 show considerable overlap with early cytoskeletal abnormalities suggesting that the alteration in signal transduction molecules is a concurrent, if not preceding, event in the pathogenesis of Alzheimer's disease. Taken together with the cell cycle abnormalities previously reported, these findings suggest that a signal derived from the cell surface contributes to a stimulus for neurons in Alzheimer's disease to re-enter the cell cycle.     

Use of semantic context by patients with Alzheimer's disease.

Used semantic-priming procedures to examine limitations in the use of semantic context by 18 patients (mean age 68.9 yrs) with Alzheimer's disease (AD) and to determine whether any such contextual effects were mediated solely through automatic processes or whether attentional processes were also involved. Three tasks were applied to examine the effect of semantic context on the performance of 18 normal elderly Ss (mean age 67.2 yrs), 18 normal young Ss (mean age 24.1 yrs), and the AD Ss. When normal and AD Ss were asked to decide whether a given item was a member of a certain category, their response times were equally affected by the item's dominance in the category. The time that AD Ss took to recognize a word was actually affected more by the semantic context provided by a priming sentence than was that of normal Ss. When asked to generate the final word of an incomplete sentence, AD Ss performed very poorly unless potential responses were highly constrained by sentence context. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intact text-specific implicit memory in patients with Alzheimer's disease.

The ability of patients with Alzheimer's disease (AD) to acquire and retain text-specific knowledge was investigated in a rereading study. Ten AD patients (aged 59–84 yrs) and 10 normal control Ss read 2 passages 3 times, each as quickly as possible, and answered recognition memory questions after the 3rd reading of each passage. The AD patients had poor explicit memory as evidenced by impaired recognition memory for the passages. In contrast, normal decreases in the times required for successive readings of each passage for AD patients indicated intact implicit memory for the passages. The absence of facilitation across passages indicated that the rereading effect was text specific, suggesting that AD patients may retain the ability to form certain kinds of implicit new associations. Alternative accounts of the mechanism underlying text-specific priming, and of the nature of intact and impaired implicit memory in AD, are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Propionibacterium acnes in the cortex of patients with Alzheimer's disease

Propionibacterium acnes was found in the cortex of three patients with Alzheimer's disease and in one frontal cortex of an elderly patient with cardiovascular risk factors and hypoxia due to a large glioblastoma of the right frontal lobe with severely increased intracranial pressure. Propionibacterium acnes is an atypical anaerobic bacterium which is sensitive to cephalosporins, but insensitive to metronidazole. It is concluded that a capillary microangiopathy (in consequence of old age and cardiovascular risk factors such as high blood pressure) leads to cortical hypoxia and reduced resistance of the cortical immune system. Prevention by dietary regimes counteracting microangiopathy and treatment with cephalosporins are recommended.