Intensity warping for multisite MRI harmonization.

In multisite neuroimaging studies there is often unwanted technical variation across scanners and sites. These "scanner effects" can hinder detection of biological features of interest, produce inconsistent results, and lead to spurious associations. We propose mica (multisite image harmonization by cumulative distribution function alignment), a tool to harmonize images taken on different scanners by identifying and removing within-subject scanner effects. Our goals in the present study were to (1) establish a method that removes scanner effects by leveraging multiple scans collected on the same subject, and, building on this, (2) develop a technique to quantify scanner effects in large multisite studies so these can be reduced as a preprocessing step. We illustrate scanner effects in a brain MRI study in which the same subject was measured twice on seven scanners, and assess our method's performance in a second study in which ten subjects were scanned on two machines. We found that unharmonized images were highly variable across site and scanner type, and our method effectively removed this variability by aligning intensity distributions. We further studied the ability to predict image harmonization results for a scan taken on an existing subject at a new site using cross-validation.

Longitudinal quantitative magnetic resonance imaging in adrenomyeloneuropathy.

BACKGROUND AND PURPOSE: Adrenomyeloneuropathy (AMN) is the most frequent metabolic hereditary spastic paraplegia. Accordingly, its main site of pathological changes is the spinal cord. It is difficult to quantify AMN progression because commonly used clinical scales have limitations and reliable biomarkers are lacking. The goal was to investigate whether spinal cord and brain quantitative magnetic resonance imaging may assess structural changes in AMN over a relatively short time period. METHODS: In this longitudinal observational study, the total cord areas (TCAs) from the C2-C3 to T2-T3 level and diffusion tensor imaging (DTI) metrics of the cervical spinal cord and brain portion of the corticospinal tracts in six AMN and six age-matched control subjects at baseline and at a mean follow-up of 22.6 months were assessed. RESULTS: A significant reduction of the mean TCA at the T1-T2 level (-3.79%) and a trend of reduction at the lowest cervical levels were observed only in AMN patients. Additionally, DTI metrics revealed significant changes in fractional anisotropy (-8.84%), mean diffusivity (+12.62%) and radial diffusivity (+25.91%) at the C2-C3 level. DISCUSSION: The study encourages the assessment of TCAs and spinal cord DTI metrics as surrogate outcome measures in AMN, by focusing on the cervical-thoracic junction and the uppermost part of the cervical spinal cord. Despite the limitation of the results due to the small number of investigated subjects, these observations are useful for forthcoming clinical trials in AMN and possibly other hereditary diseases with predominant spinal cord involvement.

Spinal cord microstructure integrating phase-sensitive inversion recovery and diffusional kurtosis imaging.

PURPOSE: The aim of this prospective study was to determine the feasibility in terms of repeatability and reproducibility of diffusional kurtosis imaging (DKI) for microstructural assessment of the normal cervical spinal cord (cSC) using a phase-sensitive inversion recovery (PSIR) sequence as the anatomical reference for accurately defining white-matter (WM) and gray-matter (GM) regions of interests (ROIs). METHODS: Thirteen young healthy subjects were enrolled to undergo DKI and PSIR sequences in the cSC. The repeatability and reproducibility of kurtosis metrics and fractional anisotropy (FA) were calculated in GM, WM, and cerebral-spinal-fluid (CSF) ROIs drawn by two independent readers on PSIR images of three different levels (C1-C4). The presence of statistically significant differences in DKI metrics for levels, ROIs (GM, WM, and CSF) repeatability, reproducibility, and inter-reader agreement was evaluated. RESULTS: Intra-class correlation coefficients between the two readers ranged from good to excellent (0.75 to 0.90). The inferior level consistently had the highest concordance. The lower values of scan-rescan variability for all DKI parameters were found for the inferior level. Statistically significant differences in kurtosis values were not found in the lateral white-matter bundles of the spinal cord. CONCLUSION: The integration of DKI and PSIR sequences in a clinical MR acquisition to explore the regional microstructure of the cSC in healthy subjects is feasible, and the results obtainable are reproducible. Further investigation will be required to verify the possibility to translate this method to a clinical setting to study patients with SC involvement especially in the absence of MRI abnormalities on standard sequences.

Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial.

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the North American Imaging in MS Cooperative (NAIMS) to evaluate CVS as a diagnostic biomarker for immediate translation into clinical care. Study objectives include determining the concordance of CVS and McDonald Criteria to diagnose MS, the sensitivity of CVS to detect MS in those with typical presentations, and the specificity of CVS among those with atypical presentations. The study will recruit a total of 400 participants (200 with typical and 200 with atypical presentations) across 11 sites. T2*-weighted, high-isotropic-resolution, segmented echo-planar MRI will be acquired at baseline and 24 months on 3-tesla scanners, and FLAIR* images (combination of FLAIR and T2*) will be generated for evaluating CVS. Data will be processed on a cloud-based platform that contains clinical and CVS rating modules. Imaging quality control will be conducted by automated methods and neuroradiologist review. CVS will be determined by Select6* and Select3* lesion methods following published criteria at each site and by central readers, including neurologists and neuroradiologists. Automated CVS detection and algorithms for incorporation of CVS into McDonald Criteria will be tested. Diagnosis will be adjudicated by three neurologists who served on the 2017 International Panel on the Diagnosis of MS. The CAVS-MS study aims to definitively establish CVS as a diagnostic biomarker that can be applied broadly to individuals presenting for evaluation of the diagnosis of MS.

Neurite Orientation Dispersion and Density Imaging for Assessing Acute Inflammation and Lesion Evolution in MS.

BACKGROUND AND PURPOSE: MR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations. MATERIALS AND METHODS: Twenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM. RESULTS: The orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions. CONCLUSIONS: NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.

Regional grey matter atrophy in clinically isolated syndromes at presentation.

BACKGROUND: The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of multiple sclerosis (CIS) is unclear, and whole brain or whole normalised grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and, therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability. METHODS: This study used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyse regional atrophy and perform voxel-wise correlations between volume and clinical metrics in 41 untreated CIS patients at presentation compared with 49 healthy controls. RESULTS: The results confirmed that there was no significant difference in whole normalised grey matter volume between CIS and controls, whereas VBM showed significant areas of bilateral thalamic, hypothalamic, putamen and caudate atrophy. Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores and the Multiple Sclerosis Functional Composite (MSFC) score, and that the MSFC score was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy, suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of multiple sclerosis. CONCLUSIONS: Atrophy is present in CIS patients at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MATERIALS AND METHODS: MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. RESULTS: The proposed count and the criterion standard count were highly correlated (r = 0.97, P < .001) and not significantly different (t59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated (t58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale (r = 0.35, P < .01) than lesion load (r = 0.10, P = .44) or lesion count (r = -.12, P = .36) alone. CONCLUSIONS: This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone.

Diffusion tensor MR imaging tractography of the pyramidal tracts correlates with clinical motor function in children with congenital hemiparesis.

BACKGROUND AND PURPOSE: Children with congenital hemiparesis have greater asymmetry in diffusion parameters of the pyramidal tracts compared with control subjects. We hypothesized that the asymmetry correlates with the severity of hemiparesis and that diffusion metrics would be abnormal in the affected tracts and normal in the unaffected tracts. MATERIALS AND METHODS: Fifteen patients with congenital hemiparesis and 17 age-matched control subjects were studied with diffusion tensor MR imaging tractography. Hemipareses were scored as mild, moderate, or severe. We measured tract-specific diffusion parameters (fractional anisotropy, mean, and directional diffusion coefficients) of the pyramidal tracts. We compared tract-specific parameters and asymmetry between the right and left tracts of the differing severity groups and control subjects. RESULTS: We observed many different causes of congenital hemiparesis including venous infarction, arterial infarction, and polymicrogyria. Clinical severity of hemiparesis correlated with asymmetry in fractional anisotropy (P < .0001), transverse diffusivity (P < .0001), and mean diffusivity (P < .03). With increasing severity of hemiparesis, fractional anisotropy decreased (P < .0001) and transverse diffusivity (P < .0001) and mean diffusivity (P < .02) increased in the affected pyramidal tract compared with controls. Diffusion metrics in the unaffected tract were similar to those in the control subjects. CONCLUSION: Asymmetry in fractional anisotropy, transverse diffusivity, and mean diffusivity, as well as the degree of abnormality in the actual values of the affected pyramidal tracts themselves, correlates with the severity of motor dysfunction in infants and children with congenital hemiparesis from different causes. This suggests that abnormalities detected by diffusion tensor MR imaging tractography in the affected pyramidal tract are related to the functional ability of the affected pyramidal tract, regardless of the etiology of motor dysfunction.

Volumetric Analysis from a Harmonized Multisite Brain MRI Study of a Single Subject with Multiple Sclerosis.

BACKGROUND AND PURPOSE: MR imaging can be used to measure structural changes in the brains of individuals with multiple sclerosis and is essential for diagnosis, longitudinal monitoring, and therapy evaluation. The North American Imaging in Multiple Sclerosis Cooperative steering committee developed a uniform high-resolution 3T MR imaging protocol relevant to the quantification of cerebral lesions and atrophy and implemented it at 7 sites across the United States. To assess intersite variability in scan data, we imaged a volunteer with relapsing-remitting MS with a scan-rescan at each site. MATERIALS AND METHODS: All imaging was acquired on Siemens scanners (4 Skyra, 2 Tim Trio, and 1 Verio). Expert segmentations were manually obtained for T1-hypointense and T2 (FLAIR) hyperintense lesions. Several automated lesion-detection and whole-brain, cortical, and deep gray matter volumetric pipelines were applied. Statistical analyses were conducted to assess variability across sites, as well as systematic biases in the volumetric measurements that were site-related. RESULTS: Systematic biases due to site differences in expert-traced lesion measurements were significant (P < .01 for both T1 and T2 lesion volumes), with site explaining >90% of the variation (range, 13.0-16.4 mL in T1 and 15.9-20.1 mL in T2) in lesion volumes. Site also explained >80% of the variation in most automated volumetric measurements. Output measures clustered according to scanner models, with similar results from the Skyra versus the other 2 units. CONCLUSIONS: Even in multicenter studies with consistent scanner field strength and manufacturer after protocol harmonization, systematic differences can lead to severe biases in volumetric analyses.

Demonstration by radionuclide imaging of possible vascular steal from a renal transplant.

Radionuclide studies in a renal-transplant patient with congestive heart failure suggested vascular steal from the renal allograft by a contralateral femoral arteriovenous fistula. These reliable, noninvasive diagnostic procedures have potential use in similar settings to evaluate allograft perfusion and function. Correction by removal of the fistula was demonstrated.

High-sensitivity coil array for head and neck imaging: technical note.

The purpose of this study was to develop coils for MR imaging of the head and neck region, with the aim of improving sensitivity and coverage. A head and neck phased array coil was constructed and compared with volume and temporomandibular joint surface coils for sensitivity and coverage in phantom studies. An algorithm was implemented to correct for the nonuniformity in the surface coil reception profile. Its application to high-resolution T2-weighted imaging in healthy volunteers was investigated.

Three-dimensional proton MR spectroscopic imaging of premature and term neonates.

BACKGROUND AND PURPOSE: Previous studies have primarily used single-voxel techniques to obtain MR spectra from the neonatal brain. In this study, we applied 3D MR spectroscopic imaging techniques to detect the spatial distribution of MR spectroscopic imaging-detectable compounds in premature and term infants. The goals were to test the feasibility of obtaining 3D MR spectroscopic images of newborns, assess the spatial variations of metabolite levels, and determine age-dependent differences in MR spectroscopic imaging data. METHODS: MR spectroscopic imaging data were acquired from nine premature (postconceptional age, 30-34 weeks) and eight term (postconceptional age, 38-42 weeks) neonates, all with normal clinical and neurologic outcomes. A specialized point-resolved spectroscopy sequence with very selective saturation pulses was used to select a region encompassing the majority of the brain. Phase encoding in three dimensions was performed in a 17-minute acquisition time to obtain 3D spectral arrays with a 1.0 cm(3) nominal spatial resolution. RESULTS: This study showed the feasibility of detecting the 3D distributions of choline, creatine, and N-acetylaspartate resonances in the neonatal brain. Significant spectral differences were detected among anatomic locations and between the premature and term groups. CONCLUSION: This initial study indicates that 3D MR spectroscopic imaging of the neonatal brain can detect anatomic and age-dependent variations in metabolite levels. This technique seems to be a powerful tool to assess the metabolic differences between anatomic regions and to follow the changes in cellular metabolites with brain maturation. This study also indicates the need for determining topologic and age-matched normative values before metabolic abnormalities in neonates can be accurately assessed by MR spectroscopy.

Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens.

BACKGROUND AND PURPOSE: Tumor progression is often difficult to distinguish from nonneoplastic treatment response on the basis of MR images alone. This study correlates metabolite levels measured by preoperative MR spectroscopic (MRS) imaging with histologic findings of biopsies, obtained during image-guided resections of brain mass lesions, to clarify the potential role of MRS in making this distinction. METHODS: Twenty-nine patients with brain tumors underwent high-resolution (0.2-1 cc) 3D proton MRS imaging and MR imaging before undergoing surgery; 11 had a newly diagnosed neoplasm, and 18 had recurrent disease. Surgical biopsies were obtained from locations referenced on MR images by guidance with a surgical navigation system. MR spectral voxels were retrospectively centered on each of 79 biopsy locations, and metabolite levels were correlated with histologic examination of each specimen. RESULTS: All mass lesions studied, whether attributable to tumor or noncancerous effects of previous therapy, showed abnormal MR spectra compared with normal parenchyma. When the pattern of MRS metabolites consisted of abnormally increased choline and decreased N-acetyl aspartate (NAA) resonances, histologic findings of the biopsy specimen invariably was positive for tumor. When choline and NAA resonances were below the normal range, histologic findings were variable, ranging from radiation necrosis, astrogliosis, and macrophage infiltration to mixed tissues that contained some low-, intermediate-, and high-grade tumor. CONCLUSION: This study demonstrated that 3D MRS imaging can identify regions of viable cancer, which may be valuable for guiding surgical biopsies and focal therapy. Regions manifesting abnormal MR spectra had a mixture of histologic findings, including astrogliosis, necrosis, and neoplasm.

Comparison of relative cerebral blood volume and proton spectroscopy in patients with treated gliomas.

BACKGROUND AND PURPOSE: Elevated relative regional cerebral blood volume (rCBV) reflects the increased microvascularity that is associated with brain tumors. The purpose of this study was to investigate the potential role of rCBV in the determination of recurrent/residual disease in patients with treated gliomas. METHODS: Thirty-one rCBV studies were performed in 19 patients with treated gliomas. All patients also had proton MR spectroscopy and conventional MR imaging. Regions of abnormality were identified on conventional MR images by two neuroradiologists and compared with rCBV and MR spectroscopic data. Metabolites and rCBV were quantified and compared in abnormal regions. RESULTS: In high-grade tumors, rCBV values were proportional to choline in regions of tumor and nonviable tissue. Although the presence of residual/recurrent disease was often ambiguous on conventional MR images, the rCBV maps indicated regions of elevated vascularity in all low-grade tumors and in 12 of 17 grade IV lesions. Regions of elevated and low rCBV corresponded well with spectra, indicating tumor and nonviable tissue, respectively. CONCLUSION: This study suggests that rCBV maps and MR spectroscopy are complementary techniques that may improve the detection of residual/recurrent tumor in patients with treated gliomas. Compared with the spectra, the rCBV maps may better reflect the heterogeneity of the tumor regions because of their higher resolution. The multiple markers of MR spectroscopy enable better discrimination between normal and abnormal tissue than do the rCBV maps.

Serial proton magnetic resonance spectroscopy imaging of glioblastoma multiforme after brachytherapy.

The utility of three-dimensional (3-D) proton magnetic resonance spectroscopy (1H-MRS) imaging for detecting metabolic changes after brain tumor therapy was assessed in a serial study of 58 total examinations of 12 patients with glioblastoma multiforme (GBM) who received brachytherapy. Individual proton spectra from the 3-D array of spectra encompassing the lesion showed dramatic differences in spectral patterns indicative of radiation necrosis, recurrent or residual tumor, or normal brain. The 1H-MRS imaging data demonstrated significant differences between suspected residual or recurrent tumor and contrast-enhancing radiation-induced necrosis. Regions of abnormally high choline (Cho) levels, consistent with viable tumor, were detected beyond the regions of contrast enhancement for all 12 gliomas. Changes in the serial 1H-MRS imaging data were observed, reflecting an altered metabolism following treatment. These changes included the significant reduction in Cho levels after therapy, indicating the transformation of tumor to necrotic tissue. For patients who demonstrated subsequent clinical progression, an increase in Cho levels was observed in regions that previously appeared either normal or necrotic. Several patients showed regional variations in response to brachytherapy as evaluated by 1H-MRS imaging. This study demonstrates the potential of noninvasive 3-D 1H-MRS imaging to discriminate between the formation of contrast-enhancing radiation necrosis and residual or recurrent tumor following brachytherapy. This modality may also allow better definition of tumor extent prior to brachytherapy by detecting the presence of abnormnal metabolite levels in nonenhancing regions of solid tumor.

Proliferative mass found in the gingiva.

The clinical course of peripheral ossifying fibroma is slow and the growth of most lesions is limited in size, usually up to 1.5 cm. Complaints are rare unless the surface becomes ulcerated, or the lesion compromises oral function or esthetic appearance. Treatment is surgical excision with close postoperative follow-up. Tooth extraction is seldom necessary. Proper surgical intervention, which includes excision of reactive tissue down to periosteum, affords a low recurrence rate of 14% to 16%.

Dental amalgam and cognitive function in older women: findings from the Nun Study.

The authors determined the number and surface area of occlusal dental amalgams in a group of 129 Roman Catholic sisters who were 75 to 102 years of age. Findings from this study of women with relatively homogeneous adult lifestyles and environments suggest that existing amalgams are not associated with lower performance on eight different tests of cognitive function.

Alzheimer's disease, dental amalgam and mercury.

BACKGROUND: Mercury, or Hg, is a neurotoxin that has been speculated to play a role in the pathogenesis of Alzheimer's disease, or AD. Dental amalgam releases low levels of Hg vapor and is a potential source of Hg for a large segment of the adult population. METHODS: The authors studied 68 subjects with AD and 33 control subjects without AD to determine Hg levels in multiple brain regions at autopsy and to ascertain the subjects' dental amalgam status and history. The subjects were from central Kentucky and Elm Grove, Wis. The authors conducted dental amalgam assessments during the lives of the majority of subjects and in some subjects at the time of autopsy only. The authors also determined three dental amalgam index scores--Event (placement, repair or removal of amalgam), Location and Time In Mouth--in addition to the numbers of and surface area of occlusal amalgam restorations. The authors determined Hg levels in multiple brain regions and performed full neuropathologic evaluations to confirm the normal status of the brain or the presence of AD. RESULTS: The authors found no significant association of AD with the number, surface area or history of having dental amalgam restorations. They also found no statistically significant differences in brain Hg level between subjects with AD and control subjects. CONCLUSIONS: Hg in dental amalgam restorations does not appear to be a neurotoxic factor in the pathogenesis of AD. The authors found that brain Hg levels are not associated with dental amalgam, either from existing amalgam restorations or according to subjects' dental amalgam restoration history. CLINICAL IMPLICATIONS: Dental amalgam restorations, regardless of number, occlusal surface area or time, do not relate to brain Hg levels.

Delivering dental care to nursing home and homebound patients.

The growing life expectancy has created a number of challenges for society and for the dental profession. One of these challenges is the increasing number of people, particularly those over age 85, who are considered frail and functionally impaired, who no longer can live independently or participate in the community. If the impairment is severe enough, the older adult may become home-bound or unable to leave the home without assistive aids or, less commonly, institutionalized in a nursing home. The characteristics of the homebound and nursing home resident represent a dramatic contrast from those who are the same age and living in the community: They are older, predominantly female, and have more physical and mental disabilities. In addition, there are differences in oral health characteristics, of which dentists and other health professionals need to be aware. Although there are a number of obstacles and barriers that make providing dental care more difficult for these patients, federal mandates and a growing professional response to develop initiatives for outreach and access are beginning to have an effect. Still the challenge for providing dental care to these groups remains great, and it will take a tremendous effort from many oral health professionals before significant change is evident. There are many professional and personal rewards for providing this care, and we as dental professionals must be committed to seeing that the oral health needs are met for all underserved populations in our society.

Providing dental care for patients diagnosed with Alzheimer's disease.

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