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.     

Postmortem studies in schizophrenia

The past decade has seen renewed interest in the neuropathology of schizophrenia. The advent of new postmortem techniques and functional imaging, along with a greater understanding of the neuropsychology of schizophrenia, have provided many new clues to the nature of the underlying brain dysfunction in this disorder. There has also been a greater understanding of the presence of severe cognitive dysfunction among many elderly persons with schizophrenia. In this article, a series of investigations are described that seek to answer basic questions about the neuropathology of schizophrenia, in particular as it pertains to cognitive impairment. The first study describes neuropathological findings in 100 consecutively autopsied persons with schizophrenia, the majority of whom had had detailed antemortem assessments. Results from this first study prompted the conclusion that schizophrenia is not characterized by classical, histologically identifiable neuropathology. Moreover, most cases of dementia in schizophrenia are probably not the result of neuropathologically identifiable dementing illnesses. The next four studies examined chemical markers that are altered in Alzheimer's disease and some other dementing conditions and have also been suggested to be abnormal in schizophrenia: choline acetyltransferase, catecholamines and indolamines, neuropeptides, and synaptic proteins. Schizophrenia cases as a group did not show a cholinergic deficit; nor did they differ from elderly comparison cases with respect to cortical catecholamines and indolamines. Among the schizophrenia cases, however, cognitive impairment was negatively correlated with choline acetyltransferase activity. Those with cognitive impairment showed evidence of cortical noradrenergic and serotonergic deficits. Neuropeptide deficits were also present in schizophrenia, but their pattern differed from that seen in Alzheimer's disease. Increased synaptic protein activity was found in the cingulate cortex of persons with schizophrenia, and this activity was correlated with schizophrenia symptoms. From this second series of studies, it was concluded that some biological measures in schizophrenia may be related to cognitive impairment (e.g., cortical amines), whereas others may be related to diagnosis (e.g., neuropeptide deficits). In addition, synaptic organization may correlate with schizophrenia symptoms.     

Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease

BACKGROUND: Identification of the neuropathological lesions that are most closely associated with the earliest symptoms of Alzheimer disease (AD) is crucial to the understanding of the disease process and the development of treatment strategies to affect its progress. Do the classical neuropathological lesions of AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration? DESIGN AND OUTCOME MEASURES: We examined the extent of neuritic plaque (NP) formation in 5 neocortical regions and the hippocampus, entorhinal cortex, and amygdala in 66 elderly subjects with no dementia, questionable dementia, or mild dementia as assessed using the Clinical Dementia Rating Scale (CDR). SETTING AND PATIENTS: Postmortem study of nursing home residents. RESULTS: Even questionable dementia (CDR, 0.5) was associated with a significant (P = .04) increase in neocortical NP density. The density of NPs increased further with increasing dementia severity in all brain regions examined. However, subjects with questionable dementia or definite but mild dementia did not differ significantly from each other. Density of NPs was nearly maximal in subjects with moderate dementia (CDR = 2.0), suggesting that other neuropathological changes may be responsible for cognitive deficits beyond this level. Dementia severity correlated significantly with the density of NPs in all brain regions examined (r range, 0.47-0.56; P < .001), even when subjects with a CDR of 0 were excluded. CONCLUSIONS: These findings are consistent with the hypothesis that NPs are among the earliest neuropathological lesions in AD. Even very mild or questionable dementia is associated with increased density of neocortical NPs that do not distinguish between clinically questionable vs definite dementia.     

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.     

A nonlinear mathematical model of electrically stimulated skeletal muscle

Researchers disagree as to whether Lewy body disease (LBD) constitutes a variant of Alzheimer's (AD) or Parkinson's disease (PD), or alternatively, whether it is an independent disease process. The neuropathological, genetic, and clinical characteristics of LBD are reviewed and compared to those of AD and PD. Data for 150 cases of LBD reported in the literature were compiled and grouped according to neuropathological status. Patients with pure LBD (with limited or no concurrent AD pathology) tend to present at a younger age with extrapyramidal signs followed by dementia, whereas patients with mixed LBD-AD (concurrent LB and AD pathology) are somewhat older and tend to present with dementia. The cognitive profile of LBD patients, and the relationships among LBD, AD, and PD remain unclear due to methodological limitations and the paucity of studies comparing the groups directly.     

A four year prospective study of age-related cognitive change in adults with Down's syndrome

BACKGROUND: While neuropathological studies indicate a high risk for Alzheimer's disease in adults with Down's syndrome, neuropsychological studies suggest a lower prevalence of dementia. In this study, cognitive deterioration in adults with Down's syndrome was examined prospectively over 4 years to establish rates and profiles of cognitive deterioration. METHODS: Fifty-seven people with Down's syndrome aged 30 years or older were assessed using a battery of neuropsychological tests on five occasions across 50 months. Assessments of domains of cognitive function known to change with the onset of Alzheimer related dementia were employed. These included tests of learning, memory, orientation, agnosia, apraxia and aphasia. The individual growth trajectory methodology was used to analyse change over time. RESULTS: Severe cognitive deterioration, such as acquired, apraxia and agnosia, was evident in 28.3% of those aged over 30 and a higher prevalence of these impairments was associated with older age. The rate of cognitive deterioration also increased with age and degree of pre-existing cognitive impairment. Additionally, deterioration in memory, learning and orientation preceded the acquisition of aphasia, agnosia and apraxia. CONCLUSIONS: The prevalence of cognitive impairments consistent with the presence of Alzheimer's disease is lower than that suggested by neuropathological studies. The pattern of the acquisition of cognitive impairments in adults with Down's syndrome is similar to that seen in individuals with Alzheimer's disease who do not have Down's syndrome.     

Neuropathological assessment of the lesions of significance in vascular dementia

OBJECTIVES: To better define the neuropathology of vascular dementia. METHODS: The neuropathological findings in 18 elderly, undemented subjects free of cerebrovascular disease were compared with 19 elderly undemented subjects who had cerebrovascular disease (many of whom had had a "stroke") and 24 elderly demented subjects who had cerebrovascular disease, but no other pathology to account for dementia. Cases in all groups were selected for absence or no more than very mild Alzheimer type pathology. RESULTS: Microvascular brain damage in the form of severe cribriform change and associated subcortical white matter damage and microinfarction were correlated with a history of dementia. Severe cribriform change was much more common and microinfarction somewhat more common in the demented group with vascular disease than the undemented group with vascular disease (P=0.0006 and P=0.031 respectively). Other findings of note were that congophilic angiopathy had a greater prevalence in the vascular dementia group than the control group, single cerebral infarcts were more common in the group who were undemented with vascular disease than in the group with dementia and vascular disease (P=0.0028), and the last group lacked evidence of macroscopic infarction more often than the first (P=0.034). There was a non-significant trend for the ratio of infarcted:uninfarcted tissue in one cerebral hemisphere to be higher in the group with dementia and vascular disease than in the group with vascular disease but no dementia. CONCLUSIONS: Microvascular disease, not macroscopic infarction, was the chief substrate of vascular dementia in this series of cases.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups had smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Dysfunctional uterine bleeding

Alzheimer's disease (AD) is characterized by progressive dementia and distinct neuropathology at autopsy. In order to test the relationship between dementia severity and loss of brain volumes, we prospectively documented the neurological/medical health of 26 male and 26 female controls and AD cases, and evaluated a subset of controls and AD cases using the Mini Mental State Examination (MMSE). At autopsy, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria confirmed diagnoses in 33 AD cases and 19 controls, and using unbiased stereology we quantified total volumes of cortical gray matter, subcortical grey matter including white matter, and forebrain. For ages of death between 50 to 100 years, controls showed minor cortical atrophy in the absence of cognitive decline. Cortical atrophy in AD cases was 20 to 25% greater than that in controls; AD patients dying at older ages showed less severe cortical atrophy than those dying at younger ages. Across all AD cases there was a strong correlation between cognitive performance on the Mini Mental State Examination and cortical volume loss. These findings confirm fundamental differences in the temporal patterns of cortical volume loss in aging and AD, and support cortical degeneration as the primary basis for cognitive decline in AD.     

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.     

Beta-amyloid deposition and other measures of neuropathology predict cognitive status in Alzheimer's disease

The relationship between progressive cognitive decline and underlying neuropathology associated with Alzheimer s disease (AD) is a key issue in defining the mechanisms responsible for functional loss. This has been a subject of much controversy, with separate studies comparing various clinical and neuropathological indices in AD. Further, it is difficult to compare studies with differences in histochemical staining protocols, brain regions examined, and data quantification criteria. There are many difficulties in designing a clinical-pathological correlative study involving AD patients. It is necessary to control for several key parameters. For example, a broad range of cognitively impaired subjects is needed, as well as short postmortem delays, brief intervals between cognitive testing and death, and the most sensitive detection and quantification techniques. In this study, we carefully controlled for each of these parameters to determine if there is a relationship between global cognitive dysfunction and multiple neuropathological indices. We selected 20 individuals representing a broad range of cognitive ability from normal to severely impaired based on the MMSE, Blessed IMC, and CDR. We counted plaque number, NFT number, dystrophic neurite number, and the relative extent of thioflavine positive plaques and neuritic involvement within plaques. We also quantified cortical area occupied by beta-amyloid immunoreactivity (A beta Load) and PHF-1 positive neuropil threads and tangles (PHF Load) using computer-based image analysis. Interestingly, we found that most pathologic measures correlated highly with the severity of dementia. However, the strongest predictor of premortem cognitive dysfunction on all three cognitive measures was the relative area of entorhinal cortex occupied by beta-amyloid deposition. In conclusion, our data show that in a carefully controlled correlative study, a variety of neuropathological variables are strongly correlated with cognitive impairment. Plaque related variables may be as strongly related to cognitive dysfunction as other established measures, including synapse loss, cell death and tau hyperphosphorylation, although no correlative study can demonstrate causality.     

Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians

A cohort of elderly Norwegians dying in nursing homes in the Oslo region have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer's disease (AD) cortical neuropathology and clinical evidence of dementia were used to assign cases without evidence of other confounding neuropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) densities in frontal, temporal and parietal cortex were then correlated with ApoE genotype to determine any relationship between ApoE genotype and AD pathology. Comparisons with ApoE epsilon 3, epsilon 4 and epsilon 2 allele dosage failed to show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by epsilon 4 allele dosage in the frontal cortex but not in other cortical regions. A reduction was seen in cortical NFT densities with epsilon 2 allele, though again this was not consistently significant in any of the groups. The epsilon 3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed epsilon 2/3 < epsilon 2/4 < epsilon 3/3 < epsilon 3/4 < epsilon 4/4 which had highest cortical NFT densities in all areas. By genotype, SP densities were generally of the order epsilon 2/4 < epsilon 2/3 < epsilon 3/3 < epsilon 4/4 < epsilon 3/4 though in none of the groups was this significant. Duration of disease showed no consistent effect on neuropathological burden. ApoE genotype may have an effect on determining whether individuals suffer from AD and the age at onset of disease but may only have a minimal effect on pathology burden.     

Severe pathological changes of parabrachial nucleus in Alzheimer's disease

In the first of a series of studies aimed at mapping brain stem pathological changes in patients with Alzheimer's disease (AD), we report a new finding regarding the parabrachial nucleus (PBN), a unit of paramount importance in the relay and integration of visceral and nociceptive information as well as in homeostatic control. The brains of 20 patients with AD were surveyed. The PBN contained pervasive neuropathological changes in 100% of the brains from those with early-onset dementia and in 80% from those with late-onset dementia. These changes were entirely absent in all 10 normal controls. The pathological changes of PBN, would cause autonomic dysfunction in patients with AD and perhaps contribute to the disproportionate mortality encountered in these patients.     

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.     

The effects of Alzheimer disease on driving-related abilities

Ten Alzheimer disease (AD) patients and 12 healthy elderly controls were evaluated on two tests of driving-related abilities: the Driver Performance Test (DPT) and the Driving Advisement System (DAS). Subjects were administered a battery of neuropsychological tests to determine if severity of dementia in AD correlates with driving performance. On the DPT, the AD patients scored in the average range in two of five skill areas (predicting the effects of a hazard, deciding how to avoid it); below average in two areas (searching for a hazard, executing evasive actions); and poorly in one area (identifying hazards). The elderly controls scored at an average level in all five skill areas. On the DAS, AD patients were significantly slower than the elderly controls on simple, two-choice, and conditional reaction time tests and were much slower than drivers in general. The AD patients' performances on two cognitive tests, the Mini-Mental State Examination (MMSE) and the Category Fluency Test, correlated significantly with aspects of performance on the DPT and the DAS. Although these are preliminary results from a pilot investigation, they suggest that AD patients' driving-related abilities are adversely affected by the disease and that driving-related performance tests and neuropsychological tests may be useful in assessing the impact of AD on driving.     

The time course of attentional zooming: a comparison of voluntary and involuntary allocation of attention to the levels of compound stimuli

Despite the original distinction between Alzheimer's disease (AD) and senile dementia, both are currently considered to be one single disease based on their common neuropathological findings. We have reviewed the literature to investigate whether there is proof to assume the existence of subgroups of AD. Historically, there is a division based on the age at onset. Although typical cortical symptoms may be more prominent in early onset cases they may be encountered in senile cases too. Cortical neuronal loss may be more severe in early onset patients, but hippocampal neuronal loss is equally severe in both groups. In older patients cerebral reserve is reduced by age-related neuronal loss and a small amount of AD-type lesions might be sufficient to cause dementia. Aphasia has been proposed as indicator of a subgroup. However, it probably occurs in all AD patients when the cortical degenerative process progresses. AD cases presenting with aphasia are rare and more often prove to be Pick's disease or primary progressive aphasia. Extrapyramidal signs are present in 25% of patients without neuroleptics and in 90% of all patients. They are usually of mild intensity, appear during the course of the disease and are found to be of extranigral origin. Myoclonus may also be encountered at any stage, although more frequent in early onset AD. Its presence is often associated with a more progressive course. Most AD cases are sporadic and some are familial, suggesting an autosomal dominant transmission. Molecular genetics reveals that some patients with familial early-onset AD have a mutation on chromosome 21. Other genes, probably on chromosome 19, may be associated with late onset familial cases, suggesting heterogeneity in familial AD. White matter involvement on computerized tomography or magnetic resonance imaging has been reported to be more prominent in a subgroup of AD patients, with later onset and confusional symptoms. The typical bilateral temporo-parietal hypometabolism on positron emission tomography and hypoperfusion on single photon emission computed tomography, is not found in all AD cases but may be indicative of a subgroup. Based on this review of the literature one homogeneous subgroup emerges: "probable" AD patients displaying memory disturbances with predominant cortical signs (especially aphasia), with a low prevalence of confusion and white matter involvement, exhibiting symptoms at a relatively early age but not exclusively below 65 years, and with a higher prevalence of genetic predisposition and more widespread neuropathological lesions at postmortem examination.     

Memory span procedures in Alzheimer's disease.

In a working memory framework, the forward memory span involves a subsidiary system that maintains information, and the backward span relies on a central executive system (CES) that allocates processing resources. The authors hypothesized that a measure of the CES derived from the backward span would distinguish Alzheimer's disease (AD) patients (n&≠&?9) from elderly controls without dementia (n&≠&?9), vary as a function of disease severity, and underlie other cognitive disturbances. Memory span procedures were Digit Span Forward and Backward and Visual Memory Span Forward and Backward. Derived CES measures discriminated between groups, predicted dementia severity, and predicted performance on some of the cognitive tasks examined. However, working memory subsidiary systems also appeared to be affected in AD, and some cognitive deficits in AD were independent of working memory disturbances. The visual memory span backward was the best predictor of group and of dementia severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naming in dementia secondary to Parkinson's, Huntington's, and Alzheimer's diseases

Confrontation naming problems have been found in patients with dementia secondary to Alzheimer's (AD), Huntington's (HD), and in a subset of Parkinson's disease (PD) patients with dementia. The source of the naming deficit has not been established. The "Perception" and the "Semantic Feature" theories have been proposed to explain this naming dysfunction. Subjects with dementia secondary to AD, HD, and PD were given three tasks to determine which theory best explained the source of confrontation naming problems. The three tasks including picture matching, visual recognition, and confrontation naming were given to 42 subjects with dementia secondary to AD, HD, and PD controlled for severity of dementia, and to age-matched controls. Subjects with dementia did not have significantly more difficulty matching pictures but did have more difficulty associating pictures through semantic features. Subjects with mild dementia secondary to AD and HD had significantly more confrontation naming errors than subjects with mild dementia secondary to PD and normal controls. All subjects with moderate dementia had significantly more confrontation naming errors than normal controls. Statistical power may have been limited due to the small number of subjects in each group. The source of the reduction in confrontation naming performance in subjects with dementia secondary to AD, HD, and PD originated in the deterioration of semantic fields. The perception theory was rejected as findings were consistent with the semantic feature theory.     

Why are stroke patients prone to develop dementia?

Stroke patients are more likely to develop dementia than age- and sex-matched controls but the pathogenesis of dementia remains unresolved in most of them. The aim of this review is to determine, from the available literature, the theoretical reasons for a stroke patient to become demented. We found three distinct factors that may explain the occurrence of dementia after a stroke. Firstly, post-stroke dementia may be the direct consequence of the vascular lesions of the brain: this is the most likely cause in patients with normal cognitive functions before a strategic infarct, especially in young patients, in Icelandic-type hereditary amyloid angiopathy and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Secondly, post-stroke dementia may be due to an associated asymptomatic Alzheimer pathology; the reasons for such an association are that (1) some cases of dementia occurring after a stroke are progressive and Alzheimer's disease (AD) is the most frequent cause of progressive dementia; (2) age and APOE epsilon 4 genotype are risk factors for both AD and ischaemic stroke; (3) a vasculopathy is often associated with AD. Lastly, white matter changes may also contribute to dementia because they often indicate small-vessel disease and a higher risk of stroke recurrence, and may lead to slight cognitive impairment. Finally, the summation of vascular lesions of the brain, white matter changes, and Alzheimer pathology might lead to dementia, even when each type of lesion, on its own, is not severe enough to induce dementia. Therefore, in patients followed up after a stroke, the term "post-stroke dementia" is probably more appropriate than that of vascular dementia because it includes all possible causal factors.     

Utility of ischemic scores in the differential diagnosis of Alzheimer's disease and ischemic vascular dementia

Despite new developments in the concept of vascular dementia, the Hachinski Ischemic Score (HIS) and its modified versions continue to be widely used in the clinical differentiation of Alzheimer's disease (AD) and ischemic vascular dementia (IVD). The sensitivity of the HIS and two modified versions in the diagnosis of AD, IVD, and single infarcts in a large, geriatric population with mild cognitive impairment (N = 100) was evaluated. Sensitivity for identification of AD was greater than 90% but was less than 70% for IVD. Over one third of patients with one or more infarcts on computed tomographic brain scans and 63% of mixed cases were classified as having probable AD. It is concluded that ischemic scores may be useful at predicting prevalence rates if individual case accuracy is ignored. Despite being sensitive to identifying AD, ischemic scores are insensitive to both cerebral infarction and IVD and cannot reliably exclude IVD. Finally, patients with mixed dementia should not be expected to have intermediate scores.