Rapid Progression Of Dementia Research Articles

Aβ1-42-containing platelet-derived extracellular vesicle is associated with cognitive decline in Parkinson's disease.

Cortical amyloid deposition is a common observation in Parkinson's disease dementia (PDD) patients. Aβ1-42 is linked to a more rapid progression of dementia. Platelets, which degranulate upon activation, are a primary source of Aβ. It has been repeatedly reported that peripheral extracellular vesicles (EVs) can partially reach the central nervous system. Thus, we speculate that activated platelet-derived Aβ1-42-containing EVs (PEV-Aβ1-42) play a crucial role in the cognitive decline of PD patients. The study included 189 participants: 66 with non-dementia PD, 73 with PDD, and 50 healthy controls. All participants underwent blood collection and clinical assessments. Twenty PD patients underwent re-examination and repeated blood collection 14 months later. A nano-scale flow cytometry assay was used to detect PEVs and PEV-Aβ1-42 using fluorescence-labeled CD62P and Aβ1-42 antibodies. Parkinson's disease dementia patients had higher PEV-Aβ1-42 concentrations than healthy controls (p = 0.028). The ratio of PEV-Aβ1-42 to PEV was significantly higher in PDD patients compared to those in non-dementia PD and healthy controls (p PD-ND < 0.001, p HC = 0.041). The PEV-Aβ1-42/PEV ratio appears to influence the odds of developing dementia (OR = 1.76, p < 0.001). The change in the PEV-Aβ1-42/PEV ratio was also correlated with cognitive decline over 14 months (r = -0.447, p < 0.05). The plasma PEV-Aβ1-42/PEV ratio may serve as a diagnostic and prognostic biomarker for PDD patients.

The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia.

Cognitive postscripts of COVID-19, codenamed as 'cognitive COVID' or 'brain fog,' characterized by multidomain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19. However, the impact on the already demented brain has not been studied. We aimed to assess the cognitive functioning and neuroimaging following SARS-CoV-2 infection in patients with pre-existing dementia. Fourteen COVID-19 survivors with pre-existing dementia (four with Alzheimer's disease, five with vascular dementia, three with Parkinson's disease dementia, and two with the behavioral variant of frontotemporal dementia) were recruited. All these patients had detailed cognitive and neuroimaging evaluations within three months before suffering from COVID-19 and one year later. Of the 14 patients, ten required hospitalization. All developed or increased white matter hyperintensities that mimicked multiple sclerosis and small vessel disease. There was a significant increase in fatigue (p = 0.001) and depression (p = 0.016) scores following COVID-19. The mean Frontal Assessment Battery (p < 0.001) and Addenbrooke's Cognitive Examination (p = 0.001) scores also significantly worsened. The rapid progression of dementia, the addition of further impairments/deterioration of cognitive abilities, and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., 'second hit' like infection/dysregulated immune response, and inflammation). 'Brain fog' is an ambiguous terminology without specific attribution to the spectrum of post-COVID-19 cognitive sequelae. We propose a new codename, i.e. 'FADE-IN MEMORY' (i.e., Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment).

Implications of Adverse Outcomes Associated with Antipsychotics in Older Patients with Dementia: A 2011-2022 Update.

Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.

Age-Related Chronic Diseases and Alzheimer's Disease in Texas: A Hispanic Focused Study.

The emergence of age-related chronic diseases within the United States has led to the direct increase of Alzheimer’s disease (AD) as well as other neurological diseases which ultimately contribute to the development of dementia within the general population. To be specific, age-related chronic diseases such as cardiovascular disease, high cholesterol, diabetes, and kidney disease contribute greatly to the advancement and rapid progression of dementia. Furthermore, unmodifiable risk factors such as advancing age and genetics as well as modifiable risk factors such as socioeconomic status, educational attainment, exercise, and diet further contribute to the development of dementia. Current statistics and research show that minority populations such as Hispanic Americans in the United States face the greatest burden of dementia due to the increase in the prevalence of overall population age, predisposing genetics, age-related chronic diseases, low socioeconomic status, as well as poor lifestyle choices and habits. Additionally, Hispanic Americans living within Texas and the rural areas of West Texas face the added challenge of finding appropriate healthcare services. This article will focus upon the research associated with AD as well as the prevalence of AD within the Hispanic American population of Texas and rural West Texas. Furthermore, this article will also discuss the prevalence of age-related chronic diseases, unmodifiable risk factors, and modifiable risk factors which lead to the progression and development of AD within the Hispanic American population of the United States, Texas, and rural West Texas.

Neuropsychiatric symptoms and comorbidity: Associations with dementia progression rate in a memory clinic cohort.

Neuropsychiatric symptoms (NPS) are associated with dementia severity and progression rate. NPS clusters have different neurobiological underpinnings; therefore, their effect on dementia progression may differ. Furthermore, little is known about whether individual comorbidities affect progression rate. We investigated the effect of NPS clusters and individual comorbidities on dementia progression. A memory clinic cohort with all-cause dementia (N=442) was followed for up to 3 years from diagnosis. Previously, we found trajectory groups of dementia progression in this cohort: one with slow progression and two with rapid progression. In the present study, using principal component analysis, three symptom clusters of NPS were identified on the Neuropsychiatric Inventory Questionnaire (NPI-Q): agitation, affective and psychosis symptom clusters. Data regarding comorbidity were collected by linkage to the Norwegian Patient Registry. Multinomial logistic regression was applied to explore the association between NPS clusters and comorbidity with trajectory-group membership. Adjusted for demographics, dementia aetiology, comorbidity and cognition, we found that, at the time of dementia diagnosis, for every point within the psychosis symptom cluster of the NPI-Q, the risk of rapid progression increased by 53%; for every point within the affective symptom cluster, the risk of rapid progression increased by 29%. A previous diagnosis of mental and behavioural disorders (excluding dementia) decreased the risk of rapid dementia progression by 65%. Psychosis and affective symptom clusters at the time of diagnosis were associated with rapid progression of dementia. Previous diagnoses of mental and behavioural disorders (excluding dementia) were associated with slow progression.

P 164 Parietal stroke mimicking the Heidenhain variant of Creutzfeldt-Jakob Disease

The Heidenhain variant of Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease with an occipito-parietal focus.It initially presents with visual disturbances such as visual agnosia or cortical blindness (Kropp et al., 1999).After presentation of early visual symptoms, rapid progression of dementia and death follows.While the Heidenhain variant matches neuropathological criteria of CJD, differential diagnosis from other neurological disorders using biomarkers from electroencephalography (EEG), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) reveal low sensitivity and specificity.As a consequence, these tools may lead to an erroneous diagnosis of the Heidenhain variant. We report about a 81-year old female who was transferred to the intensive care unit due to a generalized tonic-clonic seizure followed by prolonged somnolence, additionally exhibiting myoclonic jerks of the distal legs, left horizontal gaze palsy and horizontal nystagmus to the right.A history of cognitive decline including short-term memory and word-finding difficulties as well as visuospatial and visuoconstructive deficits over the last few weeks was reported. Initial EEG revealed 1.5 Hz left lateralized periodic sharp-wave and polyspike-wave complexes of high amplitude and triphasic morphology suspicious for CJD. Brain MRI showed a hyperintense lesion in the left occipito-parietal lobe on diffusion-weighted and FLAIR sequences, respectively.Protein 14-3-3 was positive in CSF (ELISA). However, RT-QuIC confirmatory test was negative.Other serum and CSF parameters including anti-neuronal antibodies were negative.Given this information, is it reasonable to consider the Heidenhain variant of CJD? The patient suffered from a cardioembolic stroke due to atrial fibrillation affecting the parietal branches of the middle cerebral artery.Edoxaban had been removed three weeks previously because of repeated falls.During ICU treatment, the patient developed a prolonged nonconvulsive status epilepticus (NCSE) characterized by deep coma without significant motor phenomena.EEG was refractory to an initial antiepileptic drug treatment, but finally returned to normal with valproate monotherapy.The patient, however, remained comatose until transfer to rehabilitation, but she regained consciousness two weeks later. This case points out that a parietal stroke with complicating NCSE may mimic the Heidenhain variant of CJD, particularly by under-recognition of so-called CJD red flags: First, the occurrence of 14-3-3 proteins is known to be positive after either acute stroke or seizures.Secondly, though increased intensity on DWI in CJD is discussed as a noninvasive biomarker, such signal abnormalities – particularly if sparing the basal ganglia – are not specific to CJD. Thirdly, NCSE patients with altered consciousness often present with localized or lateralized sharp waves of triphasic configuration.These atypical triphasic waves are considered to be of epileptic origin if they disappear following antiepileptic drug treatment as in our case (Trinka and Leitinger, 2015).

Trajectories of depressive symptoms and their relationship to the progression of dementia

BackgroundThe relationship between progression of Alzheimer's disease and depression and its underlying mechanisms has scarcely been studied. MethodsA sample of 282 outpatients with Alzheimer's disease (AD; 105 with amnestic AD and 177 with Alzheimer's dementia) from Norway were followed up for an average of two years. Assessment included Cornell Scale for Depression in Dementia and Clinical Dementia Rating Scale (CDR) at baseline and follow-up to examine the relationship between AD and depression. Additionally, MRI of the brain, CSF dementia biomarkers and APOE status were assessed at baseline. Progression of dementia was defined as the difference between CDR sum of boxes at follow-up and baseline (CDR-SB change). Trajectories of depressive symptoms on the Cornell Scale were identified using growth mixture modeling. Differences between the trajectories in regard to patients’ characteristics were investigated. ResultsThree distinct trajectories of depressive symptoms were identified: 231 (82.8%) of the patients had stable low-average scores on the Cornell Scale (Class 1); 11 (3.9%) had high and decreasing scores (Class 2); and 37 (13.3%) had moderate and increasing scores (Class 3). All classes had average probabilities over 80%, and confidence intervals were non-overlapping. The only significant characteristic associated with membership in class 3 was CDR-SB change. LimitationsNot all patients screened for participation were included in the study, but the included and non-included patients did not differ significantly. Some patients with amnestic MCI might have been misdiagnosed. ConclusionA more rapid progression of dementia was found in a group of patients with increasing depressive symptoms.

P1‐294: Coated‐platelets: A biomarker for rapid progression of dementia in Alzheimer's disease

P1‐294: Coated‐platelets: A biomarker for rapid progression of dementia in Alzheimer's disease

Association of Cerebral Emboli With Accelerated Cognitive Deterioration in Alzheimer's Disease and Vascular Dementia

Spontaneous cerebral emboli occur frequently in patients with Alzheimer's disease and vascular dementia. The authors investigated the effect of cerebral emboli on cognitive and functional decline in both Alzheimer's disease and vascular dementia patients over a 2-year period. Cerebral emboli entering the middle cerebral arteries were counted at baseline and every 6 months over the following 18 months using transcranial Doppler ultrasonography in 144 patients with dementia (Alzheimer's disease, N=84; vascular dementia, N=60). Deterioration in cognition was measured every 6 months over 2 years using the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), the Mini-Mental State Examination (to assess cognition), the Interview for Deterioration in Daily Living Activities in Dementia (to assess function), and the Neuropsychiatric Inventory (to assess behavioral and psychological symptoms). The relationship between cerebral emboli and progression of dementia was analyzed using longitudinal regression modeling, adjusted for age, sex, diagnostic subtype, age at onset of dementia, and significant vascular risk factors. Spontaneous cerebral emboli were detected in 63 (44%) dementia patients, 36 (43%) Alzheimer's disease patients, and 27 (45%) vascular dementia patients. ADAS-Cog scores revealed faster deterioration in cognitive functioning in patients with cerebral emboli over 2 years, with a mean increase in score of 15.4 in these patients, compared with only 6.0 for those without cerebral emboli. Similarly, Interview for Deterioration in Daily Living Activities in Dementia scores revealed more rapid deterioration in those with cerebral emboli, with a mean increase in score of 59.0 in these patients, compared with 17.9 for those without cerebral emboli. Neuropsychiatric Inventory scores also indicated faster decline in patients with cerebral emboli, with a mean increase in score of 12.0 in these patients, compared with a mean decrease in score of -3.8 for patients in whom no emboli were detected. Spontaneous cerebral emboli predict more rapid progression of dementia over 2 years in both Alzheimer's disease and vascular dementia. Clinical trials on the inhibition of cerebral emboli in the prevention and treatment of dementia are needed.

Complications of Subthalamic Nucleus Stimulation in Parkinson's Disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is effective for medically refractory Parkinson's disease. We retrospectively analyzed complications in 180 consecutive patients who underwent bilateral STN-DBS. Surgery-related complications were symptomatic intracerebral hemorrhage in 2, chronic subdural hematoma in 1, and transient deterioration of medication-induced psychosis in 2 patients. Device-related complications involved device infection in 5, skin erosion in 5, and implantable pulse generator malfunction in 2 patients. All of these patients required surgical repair. Surgery and device-related complications could be reduced with increased surgical experience and the introduction of new surgical equipment and technology. Treatment or stimulation-related complications were intractable dyskinesia/dystonia in 11, problematic dysarthria in 7, apraxia of eyelid opening (ALO) in 11, back pain in 10, and restless leg syndrome in 6 patients. Neuropsychiatric complications were transient mood changes in some, impulse control disorder in 2, severe depression related to excessive reduction of dopaminergic medications in 2, rapid progression of dementia in 1, and suicide attempts in 2 patients. Most complications were mild and transient. Dysarthria and ALO were the most frequent permanent sequelae after STN-DBS. Treatment-related adverse events may be caused not only by the effect of stimulation effect but also excessive reduction of dopaminergic medication, or progression of the disease. In conclusion, STN-DBS seems to be a relatively safe procedure. Although serious complications with permanent sequelae are rare, significant incidences of adverse effects occur. Physicians engaged in this treatment should have a comprehensive understanding of the probable complications and how to avoid them.

Role of Cerebral Microemboli in the Causation of Alzheimer‘s Disease and Vascular Dementia

Vascular risk factors are involved in the causation of both vascular dementia (VaD) and Alzheimer’s disease (AD), which together account for up to 80% of all dementias. Asymptomatic spontaneous cerebral emboli (SCE) have been shown to predict future risk of cerebrovascular accidents and silent strokes on MRI. Over a period of years, SCE could potentially cause progressive brain damage and dementia. Our research has shown that SCE occur more frequently in both AD and VaD compared with controls without dementia. SCE are associated with depressive symptoms and predict a more rapid progression of dementia. SCE may be a common mechanism of vascular brain damage that explains the AD, VaD and mixtures of the two. SCE may be a potentially treatable target to slow progression and possibly prevent these dementias.

Nasu-Hakola Disease (PLOSL)

The combination of bilateral lytic lesions in the bones of the lower and upper extremities and presenile dementia is characteristic of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, also known as Nasu-Hakola disease. The clinical course of this rare and fatal disorder is characterized by pathologic fractures of these often painful lesions, rapid progression of dementia, and death in the fifth decade of life. The radiographic changes may be confused with cystic angiomatosis, focal metastasizing hemangioendothelioma, or Langerhans' cell histiocytosis. We report five patients to illustrate the clinical presentation, radiographic images, psychiatric abnormalities, and new genetic findings. Three of the patients were siblings. A biopsy is not needed to confirm the diagnosis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy because of the unique combination of radiographic and neurologic features.

Proteomic analysis of oxidatively modified proteins induced by the mitochondrial toxin 3-nitropropionic acid in human astrocytes expressing the HIV protein tat

The human immunodeficiency virus (HIV)-Tat protein has been implicated in the neuropathogenesis of HIV infection. However, its role in modulating astroglial function is poorly understood. Astrocyte infection with HIV has been associated with rapid progression of dementia. Intracellularly expressed Tat is not toxic to astrocytes. In fact, intracellularly expressed Tat offers protection against oxidative stress-related toxins such as the mitochondrial toxin 3-nitroproprionic acid (3-NP). In the current study, human astrocytes expressing Tat (SVGA-Tat) and vector controls (SVGA-pcDNA) were each treated with the irreversible mitochondrial complex II inhibitor 3-NP. Proteomics analysis was utilized to identify changes in protein expression levels. By coupling 2D fingerprinting and identification of proteins by mass spectrometry, actin, heat shock protein 90, and mitochondrial single-stranded DNA binding protein were identified as proteins with increased expression, while lactate dehydrogenase had decreased protein expression levels in SVGA-Tat cells treated with 3-NP compared to SVGA-pcDNA cells treated with 3-NP. Oxidative damage can lead to several events including loss in specific protein function, abnormal protein clearance, depletion of the cellular redox-balance and interference with the cell cycle, ultimately leading to neuronal death. Identification of specific proteins protected from oxidation is a crucial step in understanding the interaction of Tat with astrocytes. In the current study, proteomics also was used to identify proteins that were specifically oxidized in SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. We found β-actin, calreticulin precursor protein, and synovial sarcoma X breakpoint 5 isoform A to have increased oxidation in control SVGA-pcDNA cells treated with 3-NP compared to SVGA-Tat cells treated with 3-NP. These results are discussed with reference to potential involvement of these proteins in HIV dementia and protection of astrocytes against oxidative stress by the HIV virus, a prerequisite for survival of a viral host cell.

Proteomics analysis of human astrocytes expressing the HIV protein Tat

Astrocyte infection in HIV has been associated with rapid progression of dementia in a subset of HIV/AIDS patients. Astrogliosis and microglial activation are observed in areas of axonal and dendritic damage in HIVD. In HIV-infected astrocytes, the regulatory gene tat is over expressed and mRNA levels for Tat are elevated in brain extracts from individuals with HIV-1 dementia. Tat can be detected in HIV-infected astrocytes in vivo. The HIV-1 protein Tat transactivates viral and cellular gene expression, is actively secreted mainly from astrocytes, microglia and macrophages, into the extracellular environment, and is taken up by neighboring uninfected cells such as neurons. The HIV-1 protein Tat released from astrocytes reportedly produces trimming of neurites, mitochondrial dysfunction and cell death in neurons, while protecting its host, the astrocyte. We utilized proteomics to investigate protein expression changes in human astrocytes intracellularly expressing Tat (SVGA-Tat). By coupling 2D fingerprinting and identification of proteins by mass spectrometry, we identified phosphatase 2A, isocitrate dehydrogenase, nuclear ribonucleoprotein A1, Rho GDP dissociation inhibitor α, β-tubulin, crocalbin like protein/calumenin, and vimentin/α-tubulin to have decreased protein expression levels in SVGA-Tat cells compared to the SVGA-pcDNA cells. Heat shock protein 70, heme oxygenase-1, and inducible nitric oxide synthase were found to have increased protein expression in SVGA-Tat cells compared to controls by slotblot technique. These findings are discussed with reference to astrocytes serving as a reservoir for the HIV virus and how Tat promotes survival of the astrocytic host.

Intracellular Human Immunodeficiency Virus Tat Expression in Astrocytes Promotes Astrocyte Survival but Induces Potent Neurotoxicity at Distant Sites via Axonal Transport

The human immunodeficiency virus (HIV)-Tat protein has been implicated in the neuropathogenesis of HIV infection. However, its role in modulating astroglial-neuronal relationships is poorly understood. Astrocyte infection with HIV has been associated with rapid progression of dementia. We thus initially transfected astrocytes with HIV proviral DNA and confirmed Tat production in these cells. Subsequently, using stably Tat-producing asytocyte cell lines, we observed that Tat promoted astrocyte survival by causing a prominent antioxidant effect and resistance to cell injury in these cells. Tat was released extracellularly where it could be taken up by other cells. Tat remained functionally active following uptake and caused long terminal repeat (LTR) transactivation in lymphocytic and astrocytic cell lines. Tat released from astrocytes caused mitochondrial dysfunction, trimming of neurites, and cell death in neurons. Tat neurotoxicity was attenuated by anti-Tat antibodies, kynurenate or heparan sulfate. The neurotoxic effects of Tat were caused at concentrations lower than that needed to cause LTR transactivation. When Tat-expressing cells were injected into the rat dentate gyrus, Tat was taken up by granule cells and transported along neuronal pathways to the CA3 region where it caused glial cell activation and neurotoxicity. The arginine-rich domain of Tat was essential for both the LTR transactivation and the neurotoxic properties of Tat. Thus HIV-Tat is a potent neurotoxin that may act at distant sites while at the same time it assures its production by preventing cell death in astrocytes where it is produced.

Frontal hypometabolism in mild Alzheimer's disease is associated with more rapid progression of dementia

Frontal hypometabolism in mild Alzheimer's disease is associated with more rapid progression of dementia

LEWY BODY DEMENTIA IN GEROPSYCHIATRY INPATIENT UNIT

Introduction: Lewy body dementia or LBD (also called Lewy body variant of Alzheimer's disease or diffuse Lewy body disease) is characterized clinically by extrapyramidal symptoms, behavioral disturbances, and a relatively rapid progression of dementia. The authors examined the prevalence and characteristics of LBD in a new university-based geriatric psychiatry inpatient unit. Methods: A new geriatric psychiatry inpatient unit was opened 1 year ago. At least one of the authors was directly responsible for the care of every one of the patients admitted.

Aphasia in senile dementia of the Alzheimer type.

We assessed language function, using a brief clinical Aphasia Battery and psychometric measures, in 150 subjects with senile dementia of the Alzheimer type (SDAT) and 83 elderly controls. Aphasia occurred only in demented subjects, and its prevalence increased with severity of dementia. Aphasia in mildly demented subjects was associated with both an earlier age of onset and more rapid progression of SDAT than in similarly demented nonaphasics. Language dysfunction in SDAT subjects was characterized by early decline in measures of comprehension and written expression, whereas other components, including oral naming, were less profoundly affected. Performance on the verbal psychometric measures, the Sentence Repetition and the Token tests, correlated strongly with Aphasia Battery scores and declined only minimally in nonaphasics, despite increasing dementia. We conclude that aphasia is a common feature of SDAT subjects and identifies a subgroup with more rapid progression of dementia. Furthermore, it represents language-specific dysfunction beyond the global cognitive impairment of SDAT.

Neuropsychological function in Alzheimer's disease. Pattern of impairment and rates of progression.

Although patients with Alzheimer's disease (AD) generally have impairments in multiple areas of cognitive function, there are those patients who appear to have neuropsychological deficits more prominent in one domain than in other domains. We examined the neuropsychological status of 86 patients with probable AD and 92 elderly control subjects and identified the patterns of impairments in the patients with AD. Independent deficits of visuoconstructional and lexical/semantic abilities were identified in a subset of patients by a principal components analysis. Individual patients were identified who were predominantly impaired in one, but not the other, neuropsychological domain. There were no striking relationships between the demographic characteristics of the patients and their pattern of deficits at the initial evaluation. There were no significant differences in age at onset or rate of progression of dementia among patients with different patterns of cognitive dysfunction. A review of the results of this and other studies suggests that the language impairment in AD may be associated with two distinct neuropsychological abnormalities: a lexical/semantic impairment that is unrelated to onset or progression of symptoms, and a syntactic impairment that may be associated with earlier onset and more rapid progression of dementia.