Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia

OBJECTIVES: Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a group of AD, FTD and VaD. METHODS: T1 weighted MRI images and 99mTc-HMPAO SPECT images were obtained from consecutive patients with FTD (n=21), AD (n=23) and VaD (n=20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. RESULTS: Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non-FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non-AD (VaD, FTD) patients. CONCLUSION: Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity.     

Common versus uncommon causes of dementia

When patients present with a dementia syndrome at a young age, the experienced clinician will automatically include uncommon dementias in the diagnostic considerations, as familial uncommon dementias due to genetic mutations frequently present as early-onset dementias. This paper highlights why uncommon dementias due to genetic mutations, although marginal in terms of prevalence numbers in the total population, are of significance in the quest to unravel the underlying cause of common dementias such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and vascular dementia (VaD).     

The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words “transcranial magnetic stimulation” or “motor cortex excitability” and “dementia” or “cognitive impairment” or “memory impairment” or “memory decline”. Cortical excitability is increased in Alzheimer’s disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical excitability has been observed in FTD, in Parkinson’s dementia and in dementia with Lewy bodies. Short-interval intracortical inhibition and controlateral silent period (cSP), two measures of gabaergic cortical inhibition, are abnormal in most dementias associated with parkinsonian symptoms. Ipsilateral silent period (iSP), which is dependent on integrity of the corpus callosum is abnormal in AD. While single TMS measure owns low specificity, a panel of measures can support the clinical diagnosis, predict progression and possibly identify earlier the “brain at risk”. In dementias, TMS can be also exploited to select and evaluate the responders to specific drugs and, it might become a rehabilitative tool, in the attempt to restore impaired brain plasticity.     

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease

OBJECTIVES: The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS: Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS: Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION: Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.     

Variability in blood-based amyloid-beta assays: the need for consensus on pre-analytical processing

The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO-SPECT, and CSF levels of amyloid-β peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.     

The role of MRI in dementia

Neuroimaging techniques aimed at studying structural changes of the brain may provide useful information for the diagnosis and the clinical management of patients with dementia. Magnetic resonance imaging (MRI) may show abnormalities amenable to surgical treatment in a significant percentage of patients with cognitive impairment. MRI may also assist the differential diagnosis in dementia associated with metabolic or inflammatory diseases.MRI has the potential to detect focal signal abnormalities which may assist the clinical differentiation between Alzheimer's disease (AD) and vascular dementia (VaD). Severe temporal atrophy, hyperintensities involving the hippocampal or insular cortex, and gyral hypointense bands are more frequently noted in AD. Basal ganglionic/thalamic hyperintense foci, thromboembolic infarctions, confluent white matter and irregular periventricular hyperintensities are more common in VaD.The high sensitivity of MRI in detecting T2 hyperintense lesions and the low specificity off white matter lesions have resulted in a poor correlation between MRI findings and both neuropathological and clinical manifestations. In particular, MRI has disclosed a series of white matter focal changes in the elderly population, which are not necessarily associated with cognitive dysfunction.The recent advent of a new MRI method sensitive to the microstructural changes of white matter, the so-called diffusion tensor imaging, may be helpful in correlating clinical manifestations with white matter abnormalities.     

Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia

OBJECTIVES: To determine whether parkinsonian symptoms in dementia with Lewy bodies (DLB) are associated with greater atrophy of the caudate nucleus in comparison with patients with Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: T1weighted MR scans were acquired in elderly patients with DLB, AD, VaD, and healthy controls. Normalised volumetric measurements of the caudate nucleus were obtained and parkinsonian symptoms rated using Hoehn and Yahr staging. RESULTS: There were no significant differences in the volume of the caudate nucleus between patients with dementia. However, the left caudate volume was significantly reduced in AD and DLB compared with controls. Parkinsonian symptoms did not correlate with caudate nucleus volume. CONCLUSIONS: Parkinsonian symptoms in DLB may be more closely coupled to neurochemical rather than structural changes in the caudate nucleus, and volumetric MRI analysis of caudate nucleus does not discriminate between patients with DLB, AD, and VaD.     

Epidemiology of non-AD dementias

Dementia is a common neurodegenerative disorder that affects about 10% of the population over 65 years of age. A distinction can be made between primary degenerative dementias and dementia secondary to other diseases. This review focuses on the primary non-Alzheimer's disease (AD) dementias: vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). VaD is after AD most frequent subtype of dementia with a prevalence of about 1%, ranging from 0 to 10% mainly depending on the age group investigated and the criteria used. Its incidence rate is between 1.5 and 4.1 per 1000 person-years, with no clear difference between men and women and with possibly a higher incidence in East Asia compared to Canada and Europe. Most of the VaD cases are sporadic although there are some rare familial forms of VaD as cerebral autosomal dominant arteriopathy with subcortical infarctions and leukoencephalopathy and familial cerebral amyloid angiopathy. Important risk factors for sporadic VaD are cerebrovascular pathology (brain infarction, white matter lesions and brain atrophy), midlife hypertension, and diabetes leading to increasing risk ratios. A protective effect is often found for education and moderate use of alcohol. The association between VaD and amyloid β, cholesterol, and statin use remains unclear yet. DLB and FTD are less frequent forms of dementia with prevalence rates of, respectively, 0.1–0.6 and 0.002–0.015%. FTD affects people in their middle age, accounting for up to 10–20% of the presenile dementia cases. About 14% of the FTD cases are caused by an autosomal dominant tau-mutation. However, since the prevalence of sporadic FTD is relatively low, population-based epidemiological studies are hard to perform and no non-genetic risk factors are known yet. DLB is a relative common form of dementia in old age accounting for 15–20% of cases in hospital autopsy case-series. The only known possible risk factor for DLB is the presence of an apolipoprotein E 4 allele.     

Temporal lobe rating scale: application to Alzheimer's disease and frontotemporal dementia

OBJECTIVES: Temporal lobe atrophy as assessed by MRI can be measured in several ways. Volumetric measurements are quantitative but very time consuming and require extensive training to perform, so are not easily transferable to clinical practice. Visual rating scales, by contrast, are quick and widely applicable. Although medial temporal lobe atrophy is well described in Alzheimer's disease (AD), it is uncertain how early these changes can be detected and whether they discriminate AD from other neurodegenerative diseases, most notably frontotemporal dementia (FTD). The objectives were (1) to develop a widely applicable temporal lobe rating scale, and (2) to characterise and quantify the patterns of temporal lobe atrophy in AD versus temporal and frontal variants of FTD. METHODS: The temporal lobe assessments were made using an established hippocampal rating scale extended to incorporate additional temporal regions. This was firstly validated with volumetric analysis and then applied to 30 probable AD, 30 FTD (consisting of 17 temporal variant (semantic dementia) and 13 frontal variant) and 18 control coronal MRI images. RESULTS: Bilateral hippocampal atrophy was found in 50% of the patients with AD. Contrary to expectations, patients with semantic dementia also had hippocampal atrophy, which for the left side exceeded that seen in AD; other regions (temporal pole, parahippocampal gyrus, and lateral temporal lobe), spared in AD, were severely atrophied in this group. The patients with frontal variant FTD occupied an intermediate position and were largely indistinguishable from AD. CONCLUSIONS: Hippocampal atrophy is, therefore, not specific for AD. Semantic dementia can be distinguished from AD, by the presence of severe bilateral atrophy of the temporal pole, parahippocampal and lateral regions. These findings have implications for the differential diagnosis of dementias.     

CT brain findings in clinical dementia investigation--underestimation of mixed dementia

Dementia has been found to display a more heterogeneous clinical picture than previously recognized. We investigated brain changes on computed tomography (CT) in a clinical dementia population consisting of 67 cases with Alzheimer's disease (AD), 13 with mixed dementia (AD and vascular dementia, VaD), 71 with VaD, and 12 cases that were not demented. Temporal cortical atrophy and atrophy around the temporal horns were more common in patients with mixed dementia compared to patients with VaD and the non-demented, respectively. Frontal white matter changes were present in 64% of AD, in 85% of mixed dementia and in 79% of VaD cases, but there were no differences between the dementia groups. Lacunes were present in almost 40% of AD cases and in 80 and 85% of VaD and mixed dementia cases, respectively. Only 14% of the VaD cases had large infarcts on the CT. We conclude that large infarcts were rare, even in VaD cases. The increased incidence of white matter changes and lacunes in AD patients strongly indicates an underestimation of the mixed dementia diagnosis. More distinct criteria for this diagnostic category are warranted.     

MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimer's disease

The aim of the study was to examine the relationship between white matter changes on magnetic resonance imaging (MRI), brain atrophy and ventricular dilation in late-life dementias. T(1)-weighted, T(2)-weighted, and proton density MRI scans were acquired in subjects with Alzheimer's disease (AD, N=25) and dementia with Lewy bodies (DLB, N=27). Total brain and ventricular volumes were measured and white matter lesions rated using a semi-quantitative scale. Periventricular hyperintensities (PVH) were found to independently correlate with advancing age and increasing ventricular dilatation in all subjects. In contrast, deep white matter hyperintensities (DWMH) did not correlate with measures of brain atrophy, ventricular dilatation or age, but were associated with a history of hypertension. These findings support the hypothesis that PVH and DWMH are pathologically diverse and that white matter change in AD and DLB may be determined by similar processes. In particular, PVH appear to be linked to atrophic processes involving ventricular enlargement and DWMH to ischaemic risk factors.     

Autoantibodies against amyloid and glial-derived antigens are increased in serum and cerebrospinal fluid of Lewy body-associated dementias

There is increasing evidence that in Lewy body-associated dementias (encompassing Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB)), the adaptive immune system is altered and the degenerative process includes glial cells in addition to neuronal structures. We therefore aimed to determine levels of autoantibodies against amyloid and glial-derived structures in these dementia types. Using a newly developed Enzyme-linked immunosorbent assay (ELISA), we measured levels of IgG autoantibodies against neuronal and glial structures in serum and cerebrospinal fluid of a total of 91 subjects (13 PDD, 14 DLB, 11 Alzheimer's disease (AD), 11 frontotemporal dementia (FTD), 11 vascular dementia patients (VaD), and 31 healthy controls). Autoantibody levels against α-synuclein, amyloid-β?? (Aβ??), myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and S100B were determined. In all groups, autoantibody levels were about three magnitudes higher in serum than in CSF. Serum autoantibody levels against α-synuclein, Aβ??, MOG, MBP, and S100B were higher in PDD/DLB compared to tau-associated dementias (AD, FTD), VaD, and controls, respectively, with most of them reaching highly significant p-values. In cerebrospinal fluid (CSF), levels of antibodies against oligodendrocyte-derived antigens (MOG, MBP) were significantly increased in PDD/DLB. Increased levels of autoantibodies against both neuronal- and glial-derived antigens in serum and CSF of Lewy body-associated dementias indicate an altered activity of the adaptive immune system in these dementia types. The potential of neural-derived IgG autoantibodies as part of a biomarker panel for the diagnosis of Lewy body-associated dementias should be further evaluated.     

Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study.

BACKGROUND: Magnetic resonance imaging (MRI) of hippocampal atrophy is a sensitive but not specific method to support the clinical diagnosis of early Alzheimer's disease (AD). We recently described our findings that atrophy of the entorhinal cortex (ERC) in frontotemporal dementia (FTD) is equal to that found in AD but that hippocampal atrophy in FTD is less than that found in AD. The MRI volumes of these structures provide a topographic representation of the region of interest. We hypothesized that two different dementias with distinct histopathologic and clinical features might, in addition to quantitative patterns, display topographically different patterns of atrophy. METHODS: We adopted a morphometric approach to monitor the pattern of atrophy of the hippocampus and the ERC by computing two-dimensional profiles from MRI volumes of the structures in control subjects and patients with FTD and AD. RESULTS: Compared with control subjects, atrophy of the hippocampus in patients with AD was diffuse. In patients with FTD, atrophy of the hippocampus was localized predominantly in the anterior hippocampus, suggesting a different pattern of hippocampal atrophy in FTD compared with AD. The amount and pattern of atrophy of the entorhinal cortex was virtually equal in both demented groups. CONCLUSIONS: This study provides novel data on the nature of medial temporal lobe atrophy in FTD. Morphometric MRI may be a useful technique for characterizing different patterns of atrophy in primary degenerative dementias in vivo.     

Relative frequencies of Alzheimer disease,Lewy body,vascular and frontotemporal dementia,and hippocampal sclerosis in the State of Florida Brain Bank

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.     

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.     

Qualitative aspects of learning, recall, and recognition in dementia

Objective:

To determine whether learning and serial position effect (SPE) differs qualitatively and quantitatively among different types of dementia and between dementia patients and controls; we also wished to find out whether interference affects it.

Materials and Methods:

We administered the Malayalam version of the Rey Auditory Verbal Learning Test (RAVLT) to 30 cognitively unimpaired controls and 80 dementia patients [30 with Alzheimer''s disease (AD), 30 with vascular dementia (VaD), and 20 with frontotemporal dementia (FTD)] with mild severity on the Clinical Dementia Rating Scale.

Results:

All groups were comparable on education and age, except the FTD group, who were younger. Qualitatively, the learning pattern and SPE (with primacy and recency being superior to intermediate) was retained in the AD, VaD, and control groups. On SPE in free recall, recency was superior to intermediate in the FTD group (P < 0.01 using Bonferroni correction). On recognition, the AD and VaD groups had more misses (P < 0.01), while the FTD group had more false positives (P < 0.01).

Conclusion:

Quantitative learning is affected by dementia. The pattern of qualitative learning remains unaltered in dementia in the early stages.     

Assessment of free and cued recall in Alzheimer’s disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test

Alzheimer’s disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients’ groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients’ groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.     

1H-MRS evaluation of metabolism in Alzheimer's disease and vascular dementia

Proton magnetic resonance spectroscopy (1H-MRS) allows major metabolites to be measured noninvasively in defined regions of the living brain, and can detect biochemical abnormalities where conventional structural imaging appears normal. MRS can be performed in 10 min as part of a clinical MRI examination. Biochemical abnormalities in Alzheimer's Disease (AD), vascular dementia (VaD) and other primary degenerative dementias have been investigated using MRS. Characteristic and consistent abnormalities in AD are decreased N-acetyl aspartate (NAA) and elevated myo-inositol (mI) in the mesial temporal and parieto-occipital cortex. These are thought to represent neuronal loss/dysfunction and gliosis, in anatomic distributions which reflect early pathological involvement and atrophy patterns in AD. Less consistent disturbances of glutamine and glutamate (Glx) and choline-containing compounds (Cho) have also been reported. Similar changes are seen in VaD; mostly in white matter, whereas in AD they predominate in cortical grey matter. The regional distribution of grey matter involvement may differ between AD and other degenerative dementias. Hence, both the nature and anatomic distribution of metabolite abnormalities contribute to diagnostic discrimination with MRS. NAA/mI ratios from short echo time spectra of the posterior cingulate region cortex discriminate reliably between AD subjects, normal individuals and those with VaD, and provides a useful clinical test, as an adjunct to structural imaging. Elevated mI is detected in mild cognitive impairment (MCI) and quantitative metabolite measures correlate with degrees of cognitive impairment in AD; these suggest a possible role for MRS in early diagnosis and for surrogate biochemical markers for monitoring disease progression and therapeutic response.     

Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia

Noncognitive behavioral and psychiatric disturbances are common in dementia and help in the clinical differentiation of the various subtypes. We studied the frequency of neuropsychiatric disturbances, their relationship to dementia severity and compared these disturbances in Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) using the 12-item Neuropsychiatric Inventory (NPI). A total of 98 patients (AD-44, VaD-31, FTD-23) were evaluated. All subjects were community dwelling at the time of evaluation. The three groups were comparable on global dementia severity and functional ability. All patients had clinically significant scores on the NPI with apathy, irritability and agitation being very common (>90% of patients). AD and VaD patients in Clinical Dementia Rating (CDR) stage 2 had significantly higher scores on the total NPI, agitation and disinhibition subscales compared to those in CDR stage 1. Mean scores in the domains of aberrant motor behavior, disinhibition and appetite/eating behavior differentiated FTD from AD and VaD. Neuropsychiatric disturbances in dementia appear to be universal with agitation, disinhibition and irritability being more frequent in the later stages. In this cohort disinhibition, aberrant motor behavior and appetite/eating disturbances could reliably differentiate AD and VaD from FTD. There were no significant differences between the neuropsychiatric profiles of AD and VaD.