Unraveling the mystery of cognitive changes in old age: correlation of neuropsychological evaluation with neuropathological findings in the extreme old

In order to understand what cognitive changes can be expected with aging versus those caused by disease, the New England Centenarian Study examined correlations between neuropsychological evaluation and neuropathological studies of centenarian subjects. Sixty-nine subjects were administered an extensive neuropsychological test battery designed for centenarians. Six brain donors from this group have subsequently died, and neuropathological studies of their brains have been performed to determine the presence of Alzheimer's disease (AD) and other pathological states. Of these six centenarians, three subjects had Clinical Dementia Rating scores of 0 and no dementia on neuropsychological testing, and subsequent neuropathology showed very limited AD changes. In fact, despite a range of neuropsychological findings, none of the subjects in this series met neuropathological criteria for a diagnosis of definite AD. Findings suggest that dementia is not inevitable with aging and that dementia in this age group is surprisingly often not attributable to AD.     

Hippocampal sclerosis contributes to dementia in the elderly

OBJECTIVE: To assess the relevance of hippocampal sclerosis (HS) to dementia in the elderly. BACKGROUND: HS is a prominent pathologic finding in some demented elderly, but the anatomic substrate and cognitive profiles of this dementia have not been well established. DESIGN/METHODS: An autopsy series, including dot-immunobinding assay to estimate neocortical synaptic density, of eight patients (three men, five women) with HS on whom extensive antemortem neuropsychological testing was available. RESULTS: Mean age at onset was 72.0 (+/-9.8) (range, 59 to 89) with a mean duration of symptoms of 6.5 (+/-2.9) years. Patients were only mildly impaired with a mean MMSE of 20.9 (+/-4.9) and a mean DRS of 103.1 (+/-12.5) at presentation. Cardiovascular disease was present in 88%, with a mean Hachinski score of 3.4 (+/-2.2). No patient had a history of seizures. Sixty-three percent had depression or depressive symptoms. Neuropsychologically, most patients presented with prominent memory and language deficits and became progressively demented. Neuropathologically, isolated HS was a rare finding; many patients had either very mild or neocortical "plaque only or plaque predominant" Alzheimer's disease (AD) in addition to HS changes. Midfrontal neocortical synaptophysin counts were significantly reduced in all HS patients compared with controls (p = 0.0006). CONCLUSIONS: In the elderly, HS can be a neuropathologic substrate of dementia. Clinically, it can be associated with a course that is difficult to distinguish from AD although cardiac disease and depression are frequent concomitants. Deterioration of cognitive function in these subjects may relate to other pathologic features such as neocortical synapse loss.     

Role of Alzheimer's type dementia among dementias of the elderly]

In the authors experience of a memory clinic, about 2/3 of the patients fulfilled the criteria for dementia and among the demented patients 2/3 had probable Alzheimer's disease. Vascular dementia is the second cause of dementia in elderly people, but two other degenerative disorders fulfilling the NINCDS-ADRDA criteria for Alzheimer disease (Mc Khann et al., 1984) account for degenerative dementia. There is now a consensus for the clinical diagnosis and the neuropathological aspects of these two diseases: Dementia with Lewy Bodies (Mc Keith et al., 1996) and fronto-temporal dementia (the Lund and Manchester groups, 1994). The authors emphasize the clinical aspects of those two diseases at an early stage in comparison with dementia of Alzheimer type.     

Improved efficiency of energy transfer to external work in chronic cardiomyoplasty based on the pressure-volume relationship

Confusion in the elderly patient is usually a symptom of delirium or dementia, but it may also occur in major depression and psychoses. Until another cause is identified, the confused patient should be assumed to have delirium, which is often reversible with treatment of the underlying disorder. Causes of delirium include metabolic disorders, infections and medications. Thyroid dysfunction, vitamin deficiencies and normal-pressure hydrocephalus are some potentially reversible causes of dementia. Major irreversible causes include Alzheimer's disease, central nervous system damage and human immunodeficiency virus infection. All but the rarest causes of confusion can usually be identified based on the complete history, medication review, physical examination, mental status evaluation and laboratory evaluation with longitudinal reevaluation.     

Elderly patients with schizophrenia exhibit infrequent neurodegenerative lesions

Immunohistochemistry and conventional stains were used to examine the brains of 10 elderly patients with both schizophrenia and dementia to characterize the neuropathology of their cognitive deterioration. Control cases included five nondemented elderly patients with schizophrenia, five age-compatible Alzheimer's disease (AD) patients, and five neurologically normal elderly patients. Only one of the patients with schizophrenia and dementia had AD, another was diagnosed with adult polyglucosan body disease, and the others were devoid of neuropathology that could account for dementia. Quantitation of immunohistochemically detected neurofibrillary tangles and senile plaques revealed similarly low counts for the normal control group and both schizophrenia groups. Typically, the neuropathological causes of dementia can be identified in up to 95% of cases, with AD accounting for 50-60%. The unexpected lack of neuropathological findings to explain the cognitive deterioration in this group of elderly patients with schizophrenia prompts speculation about alternative etiologies.     

Medical evaluation of dementia

A careful medical evaluation of each dementia patient from any age group is necessary. Dementia targeted questioning of the patients and their relatives should be accompanied by a quantitative dementia rating like the NOSGER-scale. The essential neuropsychological evaluation should be followed by a nosological differential diagnosis including a row of laboratory tests. Brain imaging is necessary only if one of the Dietch-criteria is met. Pharmaco-therapy should be considered for non-cognitive symptoms of dementia and a cholinergic therapy in cases of Alzheimer's disease. Considering the axiome of dementia: one dementia = two in need of help, the care-giver burden has to be eased by proposing sets of medico-social interventions, optimally at a family conference.     

Clinical tests of memory in dementia, depression, and healthy aging.

In Study 1, 20 elderly adults (mean age 72.7 yrs) with primary degenerative dementia or major depression were compared to 10 healthy aged controls on 3 tests of learning and memory: the Benton Visual Retention Test; a paired-associate learning test; and the object–memory evaluation (OME) developed by P. A. Fuld (1981). The sharpest distinction in performance among the groups was observed on the OME, and discriminant equations based on this test correctly classified at least 90% of the Ss. Study 2 applied the classification rules derived in the 1st investigation to an unselected series of 25 63–86 yr old geropsychiatry inpatients referred for neuropsychological evaluation. There was agreement between memory test classification and general categories of clinical discharge diagnosis (organic vs functional) for 21 of the Ss and with status at follow-up approximately 18 mo later. Predictive value computations suggested that the OME is more accurate in confirming true dementia than in detecting dementia syndromes associated with functional disorders. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Standardization of the diagnosis of dementia in the Canadian Study of Health and Aging

Standardization of diagnostic procedures for cognitive impairment in large epidemiologic surveys remains difficult. This paper reports results of diagnostic standardization in a subsample of 2,914 elderly (age 65 years+) Canadians from the Canadian Study of Health and Aging (CSHA; n = 10,263). The objectives were to measure the consistency of the CSHA diagnosis as a test of validity; to assess inter-rater reliability, and to assess the impact of neuropsychological data on the diagnosis of dementia. The CSHA clinical assessment included a nurse's examination, Modified Mini-Mental Status (3MS) exam and Cambridge Mental Disorders Examination, neuropsychological tests, medical history and examination, and laboratory investigations. A final diagnosis was reached in a consensus conference which incorporated preliminary diagnoses from both physicians and neuropsychologists. Computer algorithms, which were developed to check consistency between the clinical observations and the final diagnosis, demonstrated 98% concordance with DSM-III-R criteria for dementia and 92% with NINCDS-ADRADA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for probable Alzheimer's disease. Inter-rater agreement was high: kappa = 0.81 for dementia/no dementia; kappa = 0.74 for normal/cognitive impairment, not dementia/ dementia. Comparisons of diagnoses between raters by clinical specialty revealed few systematic differences. The impact of neuropsychological input on the physician's diagnosis was most marked in the borderline cases between diagnostic categories.     

A case of dementia

Recognition of cognitive impairment in the elderly is an important part of medical care. This will lead to the proper diagnosis and optimum treatment. Families seldom realise that the patient has dementia. Even with a high index of suspicion, the diagnosis can often be missed. The correct tool for making the diagnosis is also controversial.     

The validity of new memory complaints in the elderly

OBJECTIVE: To determine the validity of new subjective memory complaints (MCs) from individuals who previously, when without dementia, denied having MCs. DESIGN: Prospective cohort. SETTING: Longitudinal, community-based study of aging and dementia. PATIENTS: One hundred thirty-three community-dwelling elderly individuals who were part of a registry for the study of conditions related to aging in North Manhattan, NY. Patients were selected if they were initially without dementia and had completed at least 2 successive annual clinical and neuropsychological evaluations and provided their own medical history. MAIN OUTCOME MEASURES: Performance on memory tests--the Buschke Selective Reminding Test and a visual memory task--and global performance on a neuropsychological test battery and clinical evaluation, by which questionable dementia or dementia was diagnosed according to a well-defined paradigm. RESULTS: Fifty-three subjects with MCs at the initial evaluation performed no worse on the memory test than the 80 subjects who denied MCs initially. There was a weak association between MCs and the diagnosis of questionable dementia at baseline (P = .04), but this was nonsignificant after adjusting for age and education. At 1-year follow-up, 21 of the 80 without baseline MCs now reported MCs. At the follow-up evaluation, these 21 subjects performed significantly worse on the memory tests, were 5 times more likely to have significant cognitive impairment, and had shown significantly greater decline over the preceding year on several of the cognitive measures than the 59 who continued to deny MCs. CONCLUSION: New MCs from individuals, who when without dementia recently denied MCs, may suggest the presence of significant impairment of memory or cognition.     

Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF)

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.     

No increased incidence of Alzheimer's disease in elderly schizophrenics

There is currently controversy as to the morphological basis of cognitive impairment in elderly schizophrenics. In contrast to previous findings, recent studies have found no increased frequency of Alzheimer's disease (AD) pathology in elderly schizophrenics. We examined 99 consecutive autopsy cases of patients over the age of 55 years from a psychiatric hospital who met the DSM-III-R and ICD.10 criteria for schizophrenia (mean age 69.5 +/- 8.25 years; mean duration of illness 35.15 +/- 10.1 years), 56% showing moderate to severe dementia. All brains were blindly reviewed for evidence of AD using CERAD criteria and Braak staging of neuritic AD lesions. "Definite" AD (CERAD C, Braak stage V) was seen in 2 cases aged 56 and 67 years, respectively [2% of total or 1/68 (1.4%) of those over age 65]. "Probable" AD (CERAD B, Braak stages IV-V) were seen in 5 cases aged 71-89 years (mean 79 years; 5% of total or 7.3% of those over age 65), and 1 case each with multiple cerebral infarcts and with Parkinson's disease pathology. In addition, 2 females aged 82 and 89 years, respectively, revealed senile dementia with tangles (NIA, CERAD negative; Braak stage IV), 1 with hippocampal sclerosis. The total incidence of definite and probable AD in this cohort was 7.1% or 8.7% for those over age 65. This is in line with other recent studies showing that the frequency of AD in elderly schizophrenics may be equal or even less than in the general population. The reasons for this negative association and the basis of cognitive deficits in elderly schizophrenics--those with dementia usually showing significantly lower brain weight--await further elucidation.     

Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study

BACKGROUND: Previous studies suggested a protective effect of smoking on Alzheimer's disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. METHODS: We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimer's disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. FINDINGS: During mean follow-up of 2.1 (range 1.5-3.4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2.2 [95% CI 1.3-3.6]) and Alzheimer's disease (2.3 [1.3-4.1]). Smoking was a strong risk factor for Alzheimer's disease in individuals without the APOEepsilon4 allele (4.6 [1.5-14.2]), but had no effect in participants with this allele (0.6 [0.1-4.8]). INTERPRETATION: Smoking was associated with a doubling of the risk of dementia and Alzheimer's disease. Our finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APOEepsilon4 genotype in the aetiology of Alzheimer's disease.     

Quantitative analysis of neuropathologic changes in the cerebral cortex of centenarians

1. The quantitative distribution of neurofibrillary tangles and senile plaques was studied in the brains of 65 elderly patients aged from 96 to 104 years by immunohistochemistry. 2. According to the clinical and neuropathological diagnoses, three groups of cases were considered: 19 patients with Alzheimer's disease, 22 patients with mixed dementia (vascular and degenerative) and 24 patients with no or very mild cognitive impairment. 3. Moderate to high neurofibrillary tangle densities were always present in the hippocampus and entorhinal cortex. The inferior temporal cortex was very frequently affected in demented and non-demented cases whereas the superior frontal cortex was spared in the majority of cases independently of the clinical diagnosis. Quantitatively, Alzheimer's disease cases showed significantly higher NFT densities than cases with no clinical findings of dementia only in the CA1 field of the hippocampus. 4. The hippocampus and entorhinal cortex were often devoid of senile plaques in non-demented cases while the vast majority of Alzheimer's disease cases had few SP in these regions. The frontal and temporal cortex were more frequently involved than the limbic structures in both non-demented and Alzheimer's disease cases. The SP densities in layers II and III of the inferior temporal and superior frontal cortex were significantly higher in Alzheimer's disease than in non-demented cases. 5. These observations suggest that the dementing process in nonagenarians and centenarians may differ to that described in younger demented individuals in that neurofibrillary tangles involve principally the hippocampal formation with relative sparing of the neocortex. Furthermore, they indicate that both the neurofibrillary tangle densities in the CA1 field and senile plaque densities in the superficial layers of the neocortex must be considered for the neuropathological diagnosis of Alzheimer's disease in this age group.     

Apolipoprotein E polymorphism in elderly east Africans

Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of APOE allele frequencies and dementia remain unknown in populations from developing countries. We recently initiated a project to examine APOE frequencies in non-demented and demented elderly East Africans. Blood DNA collected from two hospital-based populations showed that the APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of 65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched demented group was also 25%. Assessment of APOE genotypes in the group of elderly Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4 allele with no clear difference in frequency between demented and non-demented subjects. Our preliminary observations suggest that elderly East Africans with no apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies compared to normal ageing subjects from Western countries including African-Americans. These results appear similar to those reported in a recent study in Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4 allele may not necessarily be a risk factor in some populations of Africa.     

Prevalence of dementia in a rural setting: A report from India

A study to estimate the prevalence of dementia in a rural population was conducted in a community located on the outskirts of Madras city in South India. Seven hundred and fifty elderly 60 years of age and older, selected using the cluster sampling technique, were interviewed using the Geriatric Mental State schedule (GMS). The prevalence of dementia was 3.5%, the percentage increasing with age. These rural prevalence estimates were higher than in urban settings (WHO multicentre study on cognitive impairment and dementia in developed and developing countries, unpublished) and male/female differences were negligible. The difficulties associated with the use of the GMS in a non-literature rural population are discussed. The implications of these findings for India's growing elderly population are highlighted.     

Neuropsychologic method in diagnosis of mild dementia in elderly and senile patients

Clinical neuropsychologic investigation was performed in 95 patients of elderly and senile age with mild dementia: 20 individuals with Alzheimer's disease (AD), 25 patients with senile dementia of Alzheimer's type (SDAT), 25 patients with vascular dementia (VD) and 25 patients with combined dementia of vascular and Alzheimer's types (DAT/VD). Clinical diagnosis of mild dementia was performed according to ICD-10. Neuropsychologic study was based on the theory and method of A.R. Luria. Syndrome of disorder of high psychic functions (HPF) in patients with mild SDAT was characterised by pathology of frontal cerebral structures and by significantly less defects of profound cerebral structures. According to the examination results the group of patients with mild AD was divided into 2 subgroups: 1) patients in which syndrome of HPF disorders was determined by pathology of parietal-temporal and profound cerebral structures and 2) patients with dysfunction of profound and frontal cerebral structures. Symptoms associated with profound cerebral structures were the main ones in patients with mild VD. Syndrome of HPF disorder included in mild DAT/VD symptoms connected with subcortical and profound brain structures as well as with frontal structures too. Besides, there were also defects in posterior frontal and parietal structures of the brain.     

Is the diagnosis of dementia stable over time among elderly immigrant Gujaratis in the United Kingdom (Leicester)?

BACKGROUND: The single largest ethnic elder group in the United Kingdom originates from the Indian subcontinent and their numbers are increasing. METHOD: Elderly Gujarati subjects, with a diagnosis of dementia ascertained during an epidemiological field study in Leicester, were reexamined at a median follow-up interval of 27 months to establish stability of the original diagnosis and cognitive decline. RESULTS: Seven of the original 11 subjects with dementia were alive at the follow-up and they were reexamined by a Gujarati psychiatrist. In six of these seven subjects the diagnosis of dementia was reconfirmed with concomitant cognitive decline on the CAMDEX dementia severity index. Informant history in three of the four original dementia subjects provided evidence of cognitive decline between the original interview and death. CONCLUSION: The diagnosis of dementia in elderly Gujaratis was stable at follow-up with concurrent evidence of decline. This also provided further support for the validity and performance of the Gujarati MMSE in the original study.     

Some issues in the assessment of HIV among older adult patients.

Due to burgeoning numbers of older adults in our population and to older adults' increased participation in high-risk behaviors, clinicians can expect to see an increase in HIV infection among this age group. The assessment of HIV among older adult patients is often difficult, however, and complicated by a lack of knowledge, implicit ageist stereotypes, and negative responses in the countertransference. A review is presented of the questions for patient interviewing, neuropsychological indicators of HIV-induced dementia, typical responses in the countertransference, and techniques that promote effective patient interviewing. Methods of coping with the difficulties commonly experienced when dealing with a potential diagnosis of HIV among older adults are highlighted. Case examples that illustrate phobic countertransference in response to assessment of HIV among three elderly patients also are presented. (PsycINFO Database Record (c) 2010 APA, all rights reserved)