Biomedical subjects

D S Knopman

Publications and source records attributed to D S Knopman.

At least 19 recordsLinked to original sources

PubMed2006

Cognitive impairment in hemodialysis patients is common.

BACKGROUND: Hemodialysis patients are at high risk for cognitive impairment due to their older age and high prevalence of stroke and cardiovascular risk factors. METHODS: Using a cross-sectional design, the authors measured cognitive function in 374 hemodialysis patients aged 55 years and older and an age-matched comparison group in Minneapolis and St. Paul, MN. Cognitive performance was measured in three domains: memory, executive function, and language. Subjects were classified as having no, mild, moderate, or severe cognitive impairment. RESULTS: Of 338 subjects who completed testing in at least two of the three cognitive domains, 13.9% (95% CI 10.4, 18.1) were classified with mild impairment, 36.1% (31.0, 41.5) with moderate impairment, 37.3% (32.1, 42.7) with severe impairment, and 12.7% (9.4, 16.8) with normal cognition. Only 2.9% had a documented history of cognitive impairment. Factors associated with severe cognitive impairment on adjusted logistic regression were stroke (adjusted OR [AOR] 1.95; 95% CI 1.08, 3.49; p < 0.03), equilibrated Kt/V > 1.2 (1.67; 1.01, 2.75; p < 0.05), and education >12 years (0.32; 0.14, 0.72; p < 0.01). The AOR for severe cognitive impairment in a random sample of 101 hemodialysis patients vs an age-matched comparison group was 3.54 (1.28, 9.78; p < 0.02). CONCLUSIONS: Moderate to severe cognitive impairment is common and undiagnosed in hemodialysis patients. Further studies are needed to determine whether dialysis exacerbates the cognitive impairment attributable to underlying disease. Cognitive testing in hemodialysis patients before dialysis initiation and periodically may be warranted.

Age Distribution↗

PubMed2006

Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease.

LY450139 dihydrate, a gamma-secretase inhibitor, was studied in a randomized, controlled trial of 70 patients with Alzheimer disease. Subjects were given 30 mg for 1 week followed by 40 mg for 5 weeks. Treatment was well tolerated. Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta.

Alanine↗

PubMed2006

Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP.

OBJECTIVE: To examine the relationship between early clinical features, pathologies, and biochemistry of the frontotemporal lobar degenerations (FTLDs), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). METHODS: The authors conducted pathologic reexamination with the most recent immunohistochemistry of all cases diagnosed with FTLD, PSP, and CBD between 1970 and 2004. The authors also reviewed the early clinical features for clinical diagnosis and application of published research criteria. RESULTS: Of 127 cases analyzed, 57 had a pathologic diagnosis of FTLD, 49 PSP, and 21 CBD. Of these, 38 were clinically reclassified as frontal variant frontotemporal dementia (FTD), 13 as progressive non-fluent aphasia (PNFA), 21 as CBD-like, 33 as PSP-like, and 13 with frontotemporal dementia with coexisting motor neuron disease (FTD-MND). The authors were unable to classify nine cases. All cases of FTD-MND were tau-negative and had pathologic evidence of motor neuron degeneration. All cases classified as PSP-like or CBD-like had tau-positive pathology. Of the 13 cases with PNFA, PSP and CBD accounted for almost 70% of the cases, while FTD was almost equally divided between tau-positive and tau-negative diseases. CONCLUSION: Frontotemporal lobar degeneration, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) have overlapping clinical features. The prediction of tau-positive pathology from a CBD or PSP-like presentation is good, while the frontotemporal dementia (FTD)-motor neuron disease syndrome almost certainly predicts motor neuron degeneration. Surprisingly, PSP and CBD accounted for most cases classified as progressive non-fluent aphasia. Frontal variant FTD is an unpredictable disease in terms of its biochemistry.

Aged↗

PubMed2005

Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI.

OBJECTIVE: To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly subjects and in subjects with amnestic mild cognitive impairment (MCI). METHODS: Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Atrophy rates of four different brain structures--hippocampus, entorhinal cortex, whole brain, and ventricle--were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period. RESULTS: During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD. DISCUSSION: Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.

Age Factors↗

PubMed2005

Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease.

OBJECTIVE: To study coronary artery bypass grafting (CABG) as a risk factor for dementia and Alzheimer disease (AD) using a case-control design. METHODS: The authors used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, MN, for the 5-year period 1990 to 1994. The authors defined dementia and AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Each case was individually matched by age (+/-1 year) and sex to a person drawn randomly from the same population, and free of dementia in the index year (year of onset of dementia in the matched case). RESULTS: Among 557 dementia cases, 24 (4.3%) had undergone a CABG prior to the onset of dementia with a median lag time of 5.5 years (range = 0.1 to 15.9). Among 557 controls, 28 subjects (5.0%) had undergone a CABG prior to the index year with a median lag time 3.9 years (range = 0.1 to 12.3); OR = 0.85 (95% CI = 0.49 to 1.49; p = 0.57) for dementia and OR = 0.78 (95% CI = 0.39 to 1.56; p = 0.48) for AD. The findings did not change after adjustment for education. The perioperative courses of cases and controls were comparable. Analyses including only the 481 cases of dementia with presumed neurodegenerative or cerebrovascular etiology were also negative. CONCLUSIONS: This population-based case-control study suggests that coronary artery bypass grafting is not a major risk factor for dementia overall, or for Alzheimer disease.

Adult↗

PubMed2005

Survival in two variants of tau-negative frontotemporal lobar degeneration: FTLD-U vs FTLD-MND.

Pathologic diagnoses in frontotemporal lobar degeneration (FTLD) include tau-positive FTLD and tau-negative FTLD. Two variants of tau-negative FTLD are FTLD with motor neuron disease (FTLD-MND) and FTLD with motor neuron disease type inclusions but without motor neuron disease (FTLD-U). An analysis of patient outcomes in these cases reveals that FTLD-MND has significantly shorter survival than FTLD-U, suggesting that FTLD-MND is a more aggressive disease process.

Age of Onset↗

PubMed2005

Cerebral MRI findings and cognitive functioning: the Atherosclerosis Risk in Communities study.

OBJECTIVE: To examine the association between prevalent cerebral abnormalities identified on MRI and cognitive functioning in a predominantly middle-aged, population-based study cohort. METHODS: Cerebral MRI was performed on 1,538 individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC) cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC, and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and sulcal size were graded by trained neuroradiologists on a semiquantitative, 10-point scale. Cognitive functioning was assessed using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). RESULTS: High ventricular grade was independently associated with significantly lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., < or =10th percentile) on the DWRT. High sulcal grade was associated with a modest decrement in scores on the DWRT. The presence of coexisting high grade WMHs and silent infarcts was independently associated with lower scores on all cognitive tests and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to 6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high-grade abnormalities was associated with increased risk of impaired functioning on all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI 1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple covariates and silent infarcts. CONCLUSION: Common changes in brain morphology are associated with diminished cognitive functioning in middle-aged and young-elderly individuals.

Aged↗

PubMed2005

DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment.

The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.

Age Factors↗

PubMed2005

APOE genotype and cognitive decline in a middle-aged cohort.

BACKGROUND: Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE epsilon4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. METHODS: Change in cognitive function was examined over a 6-year period using three neuropsychological tests among four APOE genotype groups (epsilon2/2 + epsilon2/3, epsilon3/3 (referent), epsilon4/2 + epsilon4/3, epsilon4/4). The population-based sample included 1,693 African Americans and 6,202 Caucasians initially ages 47 to 68. RESULTS: There was increasingly greater cognitive decline from the epsilon2 group to the epsilon4/4 group in Caucasians for two of the three tests. The combination of APOE epsilon4 with hypercholesterolemia or diabetes showed the greatest cognitive decline. Among African Americans, only the test measuring psychomotor speed showed associations with APOE genotype. CONCLUSIONS: APOE epsilon4 is associated with greater cognitive decline in middle-aged Caucasian individuals, with a reduced decline among epsilon2 carriers. This suggests that the processes by which APOE genotype mediates dementia risk are operative well in advance of overt dementia.

Black or African American↗

PubMed2005

Late-onset frontotemporal dementia associated with progressive supranuclear palsy/argyrophilic grain disease/Alzheimer's disease pathology.

Progressive supranuclear palsy (PSP) is typically manifested by vertical supranuclear gaze palsy, frequent falls early in the disease course, axial rigidity and poor response to levodopa. Prominent anterograde memory dysfunction with subsequent impairment in other cognitive domains is characteristic of Alzheimer's disease (AD). No clear clinical syndrome has been identified in argyrophilic grain disease (AGD). Frontotemporal dementia (FTD) is characterized by apathy, emotional blunting, disinhibition, and impairment in executive functioning despite relatively preserved memory and visuospatial abilities. Cognitive deficits are known to occur in PSP; however, overt clinical FTD without parkinsonism or supranuclear gaze palsy associated with PSP pathology has rarely been documented. We report an elderly patient with the typical clinical, neuropsychometric, and neuroimaging features of FTD who had autopsy findings most consistent with PSP plus AGD and AD in limbic structures. We suggest that PSP with or without coexisting AD and AGD be included in the differential diagnosis of patients presenting with FTD.

Age of Onset↗

PubMed2005

Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia.

Progressive supranuclear palsy (PSP) is a clinicopathological entity typically presenting as an akinetic rigid syndrome with early falls, axial rigidity, vertical supranuclear gaze palsy and levodopa resistance. Pathological features consist of tau deposition in neuronal and glial cells located mainly in subcortical and brainstem structures. Rare cases with the pathological diagnosis of atypical PSP have been described in which neocortical tau deposition is more widespread than what is usually seen in typical PSP. Progressive nonfluent aphasia (PNFA) is a syndrome characterized by spontaneous nonfluent speech and early preserved comprehension of language. Apraxia of speech (AOS) is a motor speech disorder that may be a feature of PNFA. We report the clinical and pathological findings of four cases that presented with features most consistent with PNFA predominated by AOS. Pathological features in these four cases included the typical features of PSP subcortically and in brainstem structures, but combined with tau-positive neuronal and glial pathology in the neocortex. Comprehensive semiquantitative analyses of tau burden including neurofibrillary tangles and pretangles, coiled bodies, tufted astrocytes and threads were undertaken in the four cases of atypical PSP and compared to 10 cases of typical PSP. Semiquantitative analysis demonstrated that in atypical PSP, the pathology shifts from subcortical grey and brainstem regions, commonly affected in typical PSP, towards neocortical regions. This shift in pathology accounts for the presentation of PNFA and AOS observed in our patients, as well as the lack of classic features of PSP. These cases demonstrate that atypical PSP can present as AOS and PNFA without the classic features of PSP.

Adult↗

PubMed2004

1H MR spectroscopy in common dementias.

OBJECTIVE: To determine the 1H MR spectroscopic (MRS) findings and intergroup differences among common dementias: Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). METHODS: The authors consecutively recruited 206 normal elderly subjects and 121 patients with AD, 41 with FTLD, 20 with DLB, and 8 with VaD. The 1H MRS metabolite ratio changes in common dementias were evaluated with respect to normal and also differences among the common dementias. RESULTS: N-acetylaspartate (NAA)/creatine (Cr) was lower than normal in patients with AD, FTLD, and VaD. Myo-inositol (mI)/Cr was higher than normal in patients with AD and FTLD. Choline (Cho)/Cr was higher than normal in patients with AD, FTLD, and DLB. There were no metabolite differences between patients with AD and FTLD or between patients with DLB and VaD. NAA/Cr was lower in patients with AD and FTLD than DLB. MI/Cr was higher in patients with AD and FTLD than VaD. MI/Cr was also higher in patients with FTLD than DLB. CONCLUSIONS: NAA/Cr levels are decreased in dementias that are characterized by neuron loss, such as AD, FTLD, and VaD. MI/Cr levels are elevated in dementias that are pathologically characterized by gliosis, such as AD and FTLD. Cho/Cr levels are elevated in dementias that are characterized by a profound cholinergic deficit, such as AD and DLB.

Acetylcholine↗

PubMed2004

Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy.

OBJECTIVE: To examine the clinical, genetic, and neuropathologic features of posterior cortical atrophy (PCA). DESIGN/METHODS: Using a broad definition of PCA as a syndrome with the insidious onset of visual dysfunction in the absence of primary ophthalmologic causes, the authors identified and then reviewed the presenting signs and symptoms, ApoE genotypes, tau haplotypes, and neuropathologic findings when available of PCA cases from two dementia research centers collected over the past 14 years. RESULTS: The authors identified 40 PCA cases. Their mean age at symptom onset was 60.5 +/- 8.9 years. There were twice as many women as men in the series. The principal types of visual impairment were simultanagnosia (82%) and visual field defect (47.5%). Acalculia, alexia, and anomia were also common. Insight was preserved in almost all (95%) early in the disorder. Neither apoE epsilon4 nor tau haplotype frequencies were different from typical Alzheimer disease (AD). Nine patients had died and underwent postmortem examination. Seven autopsied cases had AD pathology but when compared to typical AD, the neurofibrillary tangle (NFT) densities were significantly higher in Brodmann areas 17 and 18 (p < 0.05) and significantly lower in the hippocampus (p < 0.05). Two cases had corticobasal degeneration with maximal involvement of tau positive glial pathology in the posterior parietal lobe and Brodmann areas 17 and 18. CONCLUSIONS: PCA is a distinctive dementia syndrome in which the most pronounced pathologic involvement is in the occipitoparietal regions independent of the specific underlying pathology. AD was the most common pathologic cause, but its regional distribution differed from typical AD.

Adult↗

PubMed2004

Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD.

OBJECTIVE: To correlate different methods of measuring rates of brain atrophy from serial MRI with corresponding clinical change in normal elderly subjects, patients with mild cognitive impairment (MCI), and patients with probable Alzheimer disease (AD). METHODS: One hundred sixty subjects were recruited from the Mayo Clinic Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry Studies. At baseline, 55 subjects were cognitively normal, 41 met criteria for MCI, and 64 met criteria for AD. Each subject underwent an MRI examination of the brain at the time of the baseline clinical assessment and then again at the time of a follow-up clinical assessment, 1 to 5 years later. The annualized changes in volume of four structures were measured from the serial MRI studies: hippocampus, entorhinal cortex, whole brain, and ventricle. Rates of change on several cognitive tests/rating scales were also assessed. Subjects who were classified as normal or MCI at baseline could either remain stable or convert to a lower-functioning group. AD subjects were dichotomized into slow vs fast progressors. RESULTS: All four atrophy rates were greater among normal subjects who converted to MCI or AD than among those who remained stable, greater among MCI subjects who converted to AD than among those who remained stable, and greater among fast than slow AD progressors. In general, atrophy on MRI was detected more consistently than decline on specific cognitive tests/rating scales. With one exception, no differences were found among the four MRI rate measures in the strength of the correlation with clinical deterioration at different stages of the disease. CONCLUSIONS: These data support the use of rates of change from serial MRI studies in addition to standard clinical/psychometric measures as surrogate markers of disease progression in AD. Estimated sample sizes required to power a therapeutic trial in MCI were an order of magnitude less for MRI than for change measures based on cognitive tests/rating scales.

Aged↗

PubMed2004

The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994.

The records-linkage system of the Rochester Epidemiology Project was used to ascertain incident cases of frontotemporal lobar degeneration (FTLD) in Rochester, MN, from 1990 through 1994. Four cases of FTLD were identified (all women); two were confirmed neuropathologically. All were of the behavioral-dysexecutive type and had onset before age 70. The incidence rates (new cases per 100,000 person-years) were 2.2 for ages 40 to 49, 3.3 for ages 50 to 59, and 8.9 for ages 60 to 69. For comparison, the corresponding rates for Alzheimer disease were 0.0, 3.3, and 88.9.

Adult↗

PubMed2003

Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism.

OBJECTIVE: To determine if synucleinopathy pathology is related to REM sleep behavior disorder (RBD) plus dementia or parkinsonism. METHODS: The clinical and neuropathologic findings were analyzed on all autopsied cases evaluated at Mayo Clinic Rochester from January 1990 to April 2002 who were diagnosed with RBD and a neurodegenerative disorder. Ubiquitin and/or alpha-synuclein immunocytochemistry was used in all cases. The clinical and neuropathologic diagnoses were based on published criteria. RESULTS: Fifteen cases were identified (14 men). All had clear histories of dream enactment behavior, and 10 had RBD confirmed by polysomnography. RBD preceded dementia or parkinsonism in 10 (66.7%) patients by a median of 10 (range 2 to 29) years. The clinical diagnoses included dementia with Lewy bodies (DLB) (n = 6); multiple-system atrophy (MSA) (n = 2); combined DLB, AD, and vascular dementia (n = 1); dementia (n = 1); dementia with parkinsonism (n = 1); PD (n = 1); PD with dementia (n = 1); dementia/parkinsonism/motor neuron disease (n = 1); and AD/Binswanger's disease (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD) in 12 (neocortical in 11 and limbic in 1) and MSA in 3. Three also had argyrophilic grain pathology. In the LBD cases, concomitant AD pathology was present in six (one also with Binswanger's pathology, and one also with multiple subcortical infarcts). CONCLUSION: In the setting of degenerative dementia or parkinsonism, RBD often reflects an underlying synucleinopathy.

Age of Onset↗

PubMed2003

Neuropathology of cognitively normal elderly.

Despite general agreement about the boundaries of Alzheimer disease (AD), establishing a maximum limit for Alzheimer-type pathology in cognitively intact individuals might aid in defining more precisely the point at which Alzheimer pathology becomes clinically relevant. In this study, we examined the neuropathological changes in the brains of 39 longitudinally followed. cognitively normal elderly individuals (24 women, 15 men; age range 74-95, median 85 years). Neuropathological changes of the Alzheimer type were quantified by determining neurofibrillary tangle (NFT) staging by the method of Braak and Braak and by quantification of the abundance of diffuse, cored, and neuritic plaque burden using the scheme developed by the Consortium to Establish a Registry for Alzheimer Disease (CERAD). Vascular, Lewy body, and argyrophilic grain pathology were also assessed. We found 34 subjects (87%) with a Braak stage <IV; 32 subjects (82%) with less than moderate numbers of cored plaques and 37 subjects (95%) with less than moderate numbers of tau-positive neuritic plaques. Many subjects had moderate or frequent diffuse plaques (n = 19, 49%). By the National Institute on Aging-Reagan Institute (NIA-RI) criteria, none of our cases met criteria for high "likelihood" of AD. Four met NIA-RI criteria for intermediate "likelihood." Seven cases met CERAD criteria for possible AD. Nineteen met Khachaturian criteria for AD. Only 1 subject had neocortical Lewy bodies. Small, old infarcts were common, but no subjects had more than 2 of these and none had a single large infarction. Thus, the majority of individuals who are cognitively normal near the time of their death have minimal amounts of tau-positive neuritic pathology (Braak stage <IV and neuritic plaques <6 per x100 field in the most affected neocortical region). The few subjects with more severe AD pathology can be expected based on incidence rates of AD in the very elderly.

Aged↗

PubMed2001

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

Dementia↗