Axenfeld-Rieger Anomaly and Neuropsychiatric Problems-More than Meets the Eye.

OBJECTIVE: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients. CASE STUDY: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively. CONCLUSION: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease.

The effect of age of first exposure to competitive fighting on cognitive and other neuropsychiatric symptoms and brain volume.

It has long been established that fighting sports such as boxing and mixed martial arts can lead to head injury. Prior work from this group on the Professional Fighters Brain Health Study found that exposure to repetitive head impacts is associated with lower brain volumes and decreased processing speed in fighters. Current and previously licensed professional fighters were recruited, divided into active and retired cohorts, and matched with a control group that had no prior experience in sports with likely head trauma. This study examined the relationship between age of first exposure (AFE) to fighting sports and brain structure (MRI regional volume), cognitive performance (CNS Vital Signs, iComet C3), and clinical neuropsychiatric symptoms (PHQ-9, Barratt Impulsiveness Scale). Brain MRI data showed significant correlations between earlier AFE and smaller bilateral hippocampal and posterior corpus callosum volumes for both retired and active fighters. Earlier AFE in active fighters was correlated with decreased processing speed and decreased psychomotor speed. Retired fighters showed a correlation between earlier AFE and higher measures of depression and impulsivity. Overall, the results help to inform clinicians, governing bodies, parents, and athletes of the risks associated with beginning to compete in fighting sports at a young age.

The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis.

Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.

Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission.

The Shank3 gene encodes a scaffolding protein that anchors multiple elements of the postsynaptic density at the synapse. Previous attempts to delete the Shank3 gene have not resulted in a complete loss of the predominant naturally occurring Shank3 isoforms. We have now characterized a homozygous Shank3 mutation in mice that deletes exon 21, including the Homer binding domain. In the homozygous state, deletion of exon 21 results in loss of the major naturally occurring Shank3 protein bands detected by C-terminal and N-terminal antibodies, allowing us to more definitively examine the role of Shank3 in synaptic function and behavior. This loss of Shank3 leads to an increased localization of mGluR5 to both synaptosome and postsynaptic density-enriched fractions in the hippocampus. These mice exhibit a decrease in NMDA/AMPA excitatory postsynaptic current ratio in area CA1 of the hippocampus, reduced long-term potentiation in area CA1, and deficits in hippocampus-dependent spatial learning and memory. In addition, these mice also exhibit motor-coordination deficits, hypersensitivity to heat, novelty avoidance, altered locomotor response to novelty, and minimal social abnormalities. These data suggest that Shank3 isoforms are required for normal synaptic transmission/plasticity in the hippocampus, as well as hippocampus-dependent spatial learning and memory.

Brief report. Adult patient presenting an interstitial (9) (q21.32q31.1) direct duplication resulting from the malsegregation of a paternal balanced insertional translocation.

BACKGROUND: The partial trisomy 9q syndrome is a well-defined chromosomal disorder with over 40 reported cases in the literature. However, 9q duplications derived from an insertional translocation have rarely been reported. METHODS: Cytogenetic and molecular analyses using G-banding, fluorescence in situ hybridization, and single nucleotide polymorphism array were performed in a 25-year-old male patient with intellectual disability, behavioral abnormalities, speech delay, postnatal growth retardation, distinctive facial features, and pyloric stenosis. RESULTS: G-banding analysis showed an extra chromosome segment of unknown origin inserted into band 4q25. A 16,747,601 bp duplication of 9q21.32q31.1 inserted into band 4q25 and a balanced (4;9) insertional translocation were identified by single nucleotide polymorphism array and fluorescence in situ hybridization analysis respectively in the patient and his healthy father. A literature review was performed to refine genotype-phenotype correlation of the partial trisomy 9q syndrome. CONCLUSION: This is the first report on the molecular characterization of a partial trisomy 9q syndrome derived from an insertional translocation between nonhomologous chromosomes. Our findings provide important information for genetic counseling and prenatal diagnosis of future pregnancies in this family.

Emotional and behavioral symptoms in neurodegenerative disease: a model for studying the neural bases of psychopathology.

Disruptions in emotional, cognitive, and social behavior are common in neurodegenerative disease and in many forms of psychopathology. Because neurodegenerative diseases have patterns of brain atrophy that are much clearer than those of psychiatric disorders, they may provide a window into the neural bases of common emotional and behavioral symptoms. We discuss five common symptoms that occur in both neurodegenerative disease and psychopathology (i.e., anxiety, dysphoric mood, apathy, disinhibition, and euphoric mood) and their associated neural circuitry. We focus on two neurodegenerative diseases (i.e., Alzheimer's disease and frontotemporal dementia) that are common and well characterized in terms of emotion, cognition, and social behavior and in patterns of associated atrophy. Neurodegenerative diseases provide a powerful model system for studying the neural correlates of psychopathological symptoms; this is supported by evidence indicating convergence with psychiatric syndromes (e.g., symptoms of disinhibition associated with dysfunction in orbitofrontal cortex in both frontotemporal dementia and bipolar disorder). We conclude that neurodegenerative diseases can play an important role in future approaches to the assessment, prevention, and treatment of mental illness.

Psychiatric presentation of sporadic Creutzfeldt-Jakob disease: a challenge to current diagnostic criteria.

Pathological diagnosis remains the gold standard for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), but being able to differentiate between CJD and non-prion diseases clinically is important because many of the non-prion, rapidly progressive dementias are treatable. Diagnostic criteria need both high sensitivity and specificity while remaining applicable to clinical practice. Despite extensive updates to the clinical criteria for sCJD, there remains a heavy emphasis on neurological signs. We describe a psychiatric presentation of sCJD that did not fulfill the diagnostic criteria until very late in a prolonged disease course and required biopsy for diagnosis.

Differential putaminal morphology in Huntington's disease, frontotemporal dementia and Alzheimer's disease.

OBJECTIVE: Direct neuronal loss or deafferentation of the putamen, a critical hub in corticostriatal circuits, may result in diverse and distinct cognitive and motoric dysfunction in neurodegenerative disease. Differential putaminal morphology, as a quantitative measure of corticostriatal integrity, may thus be evident in Huntington's disease (HD), Alzheimer's disease (AD) and frontotemporal dementia (FTD), diseases with differential clinical dysfunction. METHODS: HD (n = 17), FTD (n = 33) and AD (n = 13) patients were diagnosed according to international consensus criteria and, with healthy controls (n = 17), were scanned on the same MRI scanner. Patients underwent brief cognitive testing using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Ten MRI scans from this dataset were manually segmented as a training set for the Adaboost algorithm, which automatically segmented all remaining scans for the putamen, yielding the following subset of the data: 9 left and 12 right putamen segmentations for AD; 25 left and 26 right putamina for FTD; 16 left and 15 right putamina for HD; 12 left and 12 right putamina for controls. Shape analysis was performed at each point on the surface of each structure using a multiple regression controlling for age and sex to compare radial distance across diagnostic groups. RESULTS: Age, but not sex and intracranial volume (ICV), were significantly different in the segmentation subgroups by diagnosis. The AD group showed significantly poorer performance on cognitive testing than FTD. Mean putaminal volumes were HD < FTD < AD ≤ controls, controlling for age and ICV. The greatest putaminal shape deflation was evident in HD, followed by FTD, in regions corresponding to the interconnections to motoric cortex. CONCLUSIONS: Differential patterns of putaminal atrophy in HD, FTD and AD, with relevance to corticostriatal circuits, suggest the putamen may be a suitable clinical biomarker in neurodegenerative disease.

Ferritin overexpression in Drosophila glia leads to iron deposition in the optic lobes and late-onset behavioral defects.

Cellular and organismal iron storage depends on the function of the ferritin protein complex in insects and mammals alike. In the central nervous system of insects, the distribution and relevance of ferritin remain unclear, though ferritin has been implicated in Drosophila models of Alzheimers' and Parkinsons' disease and in Aluminum-induced neurodegeneration. Here we show that transgene-derived expression of ferritin subunits in glial cells of Drosophila melanogaster causes a late-onset behavioral decline, characterized by loss of circadian rhythms in constant darkness and impairment of elicited locomotor responses. Anatomical analysis of the affected brains revealed crystalline inclusions of iron-loaded ferritin in a subpopulation of glial cells but not significant neurodegeneration. Although transgene-induced glial ferritin expression was well tolerated throughout development and in young flies, it turned disadvantageous at older age. The flies we characterize in this report contribute to the study of ferritin in the Drosophila brain and can be used to assess the contribution of glial iron metabolism in neurodegenerative models of disease.

Imaging the impact of prenatal alcohol exposure on the structure of the developing human brain.

Prenatal alcohol exposure has numerous effects on the developing brain, including damage to selective brain structure. We review structural magnetic resonance imaging (MRI) studies of brain abnormalities in subjects prenatally exposed to alcohol. The most common findings include reduced brain volume and malformations of the corpus callosum. Advanced methods have been able to detect shape, thickness and displacement changes throughout multiple brain regions. The teratogenic effects of alcohol appear to be widespread, affecting almost the entire brain. The only region that appears to be relatively spared is the occipital lobe. More recent studies have linked cognition to the underlying brain structure in alcohol-exposed subjects, and several report patterns in the severity of brain damage as it relates to facial dysmorphology or to extent of alcohol exposure. Future studies exploring relationships between brain structure, cognitive measures, dysmorphology, age, and other variables will be valuable for further comprehending the vast effects of prenatal alcohol exposure and for evaluating possible interventions.

Gray matter correlates of behavioral severity in progressive supranuclear palsy.

BACKGROUND: Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy. METHODS: We performed standardized tests of behavioral severity (Frontal Behavioral Inventory), cognitive severity (Mini-Mental State Examination), motor severity (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Part III), and a 3.0-T volumetric head magnetic resonance imaging scan in 18 prospectively recruited subjects meeting National Institute of Neurological Diseases and Stroke-Society of Progressive Supranuclear Palsy criteria for probable progressive supranuclear palsy. Atlas-based parcellation was utilized to obtain regional gray matter volumes of frontal, temporal, and parietal lobe, and caudate and putamen, and voxel-based morphometry was used to assess voxel-level gray matter loss. We performed correlation analyses between total Frontal Behavioral Inventory score and gray matter volume, as well as assessed gray matter volume across three groups defined according to behavioral severity (mild, moderate, and severe) based on total Frontal Behavioral Inventory score. RESULTS: Specific behaviors, with the exception of apathy that occurred in 83% of the subjects, were relatively infrequent. There was no association between Frontal Behavioral Inventory and cognitive or motor severity. Regions of the frontal lobe, particularly, the lateral posterior frontal cortex, significantly correlated with the total Frontal Behavioral Inventory score when using both regional volume and voxel-level analyses. The groupwise analyses also supported these findings. The presence of apathy correlated with atrophy of the putamen. DISCUSSION: Behavioral severity in progressive supranuclear palsy appears to be associated with volume loss of frontostriatal regions, in particular, lateral posterior frontal lobe and putamen.

Influence of premorbid psychopathology and lesion location on affective and behavioral disorders after ischemic stroke.

Early recognition of psychopathological symptoms (PSs) after stroke is important because they greatly influence the recovery of patients. The aim of this study was to investigate the predictive factors of PSs occurring in patients with ischemic stroke. Eighty-nine patients were prospectively evaluated upon admission and 4, 12, and 26 weeks later with the Neuropsychiatric Inventory, Hamilton's Rating Scales for Depression and Anxiety, and a battery of neuropsychological and functional scales. Depression and apathy were the most frequent PSs detected after stroke. Premorbid psychopathologies and right-hemisphere location were the main predictive indicators of early and long-term PSs.

[Do behavioural problems existing at referral become worse in subsequent years? A study of young persons referred to the outpatient unit of the mental health service]. / Wordt het probleemgedrag bij aanmelding in de loop der jaren erger? Een onderzoek bij jeugdigen verwezen naar de ambulante ggz.

BACKGROUND: Although young persons with severe and complex emotional and behavioural problems are often referred to the outpatient unit of the mental health service, little information is available about whether these problems increase over the years. This information is urgently needed in order to ensure that the mental health service provides adequate care. AIM: To obtain more insight into any increase in young persons' emotional and behavioural problems that may occur over a period of six years following referral to an outpatient unit of the mental health service. METHOD: The nature, severity and complexity of the emotional and behavioural problems of 123 young persons (1999) and of 149 young persons (2005) at the time of the referral - as rated by their parents on the basis of the Child Behavior Checklist (CBCL) - were assessed; the young persons' records were also checked for background characteristics. RESULTS: Compared to 1999, the year 2005 saw a slight decrease in the severity of the problems existing at referral; social problems also declined significantly compared to 1999. Problems identified in the 2005 group often seemed less complex than in 1999. The severity of delinquent behaviour as measured on the Delinquent Behaviour Scale seems to have risen in the 12 to 18 age group in 2005, whereas the severity declined in the 4 to 11-year olds. CONCLUSION: Emotional and behavioural problems as reported by the parents at the time their children were referred to the mental health service do not increase.

Anosognosia for behavioral disturbances in frontotemporal dementia and corticobasal syndrome: A voxel-based morphometry study.

BACKGROUND: Patients with syndromes of the frontotemporal dementia spectrum are frequently unaware of their behavioral changes. METHODS: Seventy patients with a clinical diagnosis of behavioral variant frontotemporal dementia (bv-FTD, n = 27), aphasic variant frontotemporal dementia (a-FTD, n = 12) and corticobasal syndrome (CBS, n = 31) participated in the study. Anosognosia for behavioral disturbances was measured as discrepancy between caregiver's and patient's ratings on the Frontal Systems Behavior Scale for present and premorbid behavioral symptoms. Voxel-based morphometry analysis of MRI data was performed to explore the association between anosognosia and gray matter loss. RESULTS: Although behavioral symptoms were reported in all the groups, the comparison between present and premorbid anosognosia revealed that bv-FTD patients not only underestimated their present behavioral disturbances compared to their caregivers, but also overestimated their premorbid behavioral disturbances. Across all groups, the degree of anosognosia for present behavioral impairment correlated with gray matter atrophy in a posterior region of the right superior temporal sulcus (adjacent to the temporoparietal junction). CONCLUSION: These results confirm the role of the right temporoparietal cortex in the genesis of anosognosia and suggest that, in clinical syndromes of the frontotemporal dementia spectrum, anosognosia is associated with the dysfunction of temporoparietal mechanisms of self versus others knowledge.

Vascular endothelial growth factor attenuates status epilepticus-induced behavioral impairments in rats.

Vascular endothelial growth factor (VEGF) is a vascular growth factor more recently recognized as a neurotrophic factor (for review, see Storkebaum E, Lambrechts D, Carmeliet P. BioEssays 2004;26:943-54). We previously reported that endogenous VEGF protein is dramatically upregulated after pilocarpine-induced status epilepticus in the rat, and that intra-hippocampal infusions of recombinant human VEGF significantly protected against the loss of hippocampal CA1 neurons in this model (Nicoletti JN, Shah SK, McCloskey DP, et al. Neuroscience 2008;151:232-41). We hypothesized that we would see a preservation of cognitive and emotional functioning with VEGF treatment accompanying the neuroprotection previously observed in this paradigm. Using the Morris water maze to evaluate learning and memory, and the light-dark task to assess anxiety, we found a selective profile of preservation. Specifically, VEGF completely preserved normal anxiety functioning and partially but significantly protected learning and memory after status epilepticus. To determine whether the ability of VEGF to attenuate behavioral deficits was accompanied by sustained preservation of hippocampal neurons, we stereologically estimated CA1 pyramidal neuron densities 4 weeks after status epilepticus. At this time point, we found no significant difference in neuronal densities between VEGF- and control-treated status epilepticus animals, suggesting that VEGF could have protected hippocampal functioning independent of its neuroprotective effect.

Anterior thalamic radiation integrity in schizophrenia: a diffusion-tensor imaging study.

The anterior limb of the internal capsule (ALIC) is a white matter structure, the medial portion of which includes the anterior thalamic radiation (ATR) carrying nerve fibers between thalamus and prefrontal cortex. ATR abnormalities have a possible link with cognitive abnormalities and negative symptoms in schizophrenia. We aimed to study the fiber integrity of the ATR more selectively by isolating the medial portion of the ALIC using region-of-interest based methodology. Diffusion-tensor imaging was used to measure the anisotropy of total ALIC (tALIC) and medial ALIC (mALIC) in 39 schizophrenia and 33 control participants, matched for age/gender/handedness. Relationships between anisotropy, psychopathology, and cognitive performance were analyzed. Compared with controls, schizophrenia participants had 4.55% lower anisotropy in right tALIC, and 5.38% lower anisotropy in right mALIC. There were no significant group anisotropy differences on the left. Significant correlations were observed between right ALIC integrity and relevant domains of cognitive function (e.g., executive function, working memory). Our study suggests an asymmetric microstructural change in ALIC in schizophrenia involving the right side, which is only minimally stronger in mALIC, and which correlates with cognitive impairment. Microstructural changes in the ALIC may be linked to cognitive dysfunction in schizophrenia.

Executive and behavioral deficits share common neural substrates in frontotemporal lobar degeneration - a pilot FDG-PET study.

Behavioral and executive dysfunctions are typical symptoms of frontotemporal lobar degeneration, associated with its subtypes frontotemporal and semantic dementia. Although both functions depend on the frontal lobes, no study has yet compared their neural correlates in frontotemporal lobar degeneration. Accordingly, we correlated clinical scores of behavioral and executive deficits with glucose utilization as measured by [(18)F]fluorodeoxyglucose positron emission tomography in 17 patients with frontotemporal lobar degeneration and 9 age- and sex-matched control subjects. Impairment in executive functions was measured by the Behavioral Assessment of the Dysexecutive Syndrome, a modified Stroop paradigm and/or the Tower of Toronto Test. Behavioral deficits were examined with the Neuropsychiatric Inventory. Executive dysfunction was correlated with diminished glucose utilization in frontomedial and frontolateral cortices. Brain regions included the anterior cingulate and midcingulate gyri, anterior medial frontal cortex, and left frontolateral cortex. Behavioral deficits were associated with mainly frontomedial networks, particularly the anterior medial frontal cortex, gyrus rectus, and area subcallosa. Our pilot study reveals partially overlapping neural correlates of executive and behavioral dysfunction in frontotemporal lobar degeneration. The results suggest that some behavioral deficits, namely disinhibition and appetite and eating abnormalities, are particularly related to executive dysfunction. This hypothesis might be further explored in studies involving larger patient groups.

Electroacupuncture at Baihui acupoint (GV20) reverses behavior deficit and long-term potentiation through N-methyl-d-aspartate and transient receptor potential vanilloid subtype 1 receptors in middle cerebral artery occlusion rats.

Vascular dementia is one of the most important causes that account for 20-40% of all dementia cases. The aim of this study was to investigate whether electroacupuncture can reduce behavior deficit and long-term potentiation (LTP) in vascular dementia. Here we used a middle cerebral artery occlusion (MCAo) technique to induce a vascular dementia model with additional electroacupuncture (EA) manipulation. Behaviors were impaired in animals with MCAo, and similar results were observed with long-term potentiation induction. MCAo decreased the expression of LTP from 180.4±14.9% to 112.5±18.3%, suggesting that cerebral ischemia could impair the hippocampal LTP. In addition, immunostaining results showed that the expressions of N-methyl-D-aspartate receptor subtype 1 (NR1) and transient receptor potential vanilloid subtype 1 (TRPV1) receptors were significantly increased in the hippocampal CA1 areas. Noticeably, these phenomena can be reversed by 2 Hz EA at Baihui acupoint (GV20) for six consecutive days. Our results support a rescue role of 2 Hz EA for MCAo-induced behavior and LTP impairment. These results also suggest that NMDAR1 and TRPV1 may be involved in this pathway.

Early behavioral and developmental interventions in ADNP-syndrome: A case report of SWI/SNF-related neurodevelopmental syndrome.

BACKGROUND: Autism spectrum disorder (ASD) affects approximately one in 59 children. Variants in the activity-dependent neuroprotector homeobox ADNP (OMIM #611386) gene may be one of the most common single-gene causes of syndromic ASD. Most patients diagnosed with ADNP syndrome have ASD as a comorbidity, and all patients have mild-to-severe intellectual disability. METHODS/CASE REPORT: We present a case report of a patient diagnosed with ADNP syndrome at 2.5 years of age. The patient has many of the key features of the syndrome, including ASD, global developmental delay, behavioral problems, congenital heart defect, early tooth eruption, and vision problems. The patient's initial presentation included congenital diaphragmatic hernia (CDH), which has not been previously reported in this condition. RESULTS: The patient exhibited frequent behavioral outbursts and was initiated on antipsychotic medication with near-complete resolution of symptoms allowing her to engage more fully in early intervention therapies leading to progress in language acquisition. CONCLUSION: This short report provides guidance for antipsychotic medication dosing to improve early intervention outcomes. This is the first report of CDH in this syndrome.

Impact of cerebrovascular pathology on behavioural and neuropsychiatric symptoms in patients with Alzheimer's dementia: findings from a retrospective, naturalistic study.

AIM: Cerebrovascular disease (CVD) has been associated with depression and a host of neuropsychiatric conditions including dementia. This study assessed the relationship between cerebrovascular findings reported on MRI brain scans and neuropsychiatric symptoms (NPS) and behavioural problems in patients with Alzheimer's disease (AD). METHODS: Medical notes were retrospectively reviewed in patients undergoing brain MRI following referral for cognitive impairment to a memory clinic between January 2004 and June 2008. Patients with AD were graded into four categories of CVD severity based on neuroradiology reports and assessed for behavioural and NPS and activities of daily living using Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS) and Bristol Activities of Daily Living (BADL). Frontal lobe symptoms and parkinsonian features were also evaluated. RESULTS: Of the initial 232 patients who underwent MRI 72% were diagnosed with AD. 89% of AD patients had CVD findings reported on MRI. Moderate-to-severe CVD was present in 47% of patients. None of the AD patients satisfied a diagnosis of vascular dementia. There was no significant relationship observed between level of MRI CVD findings and scores on NPI (p = 0.57), GDS (p = 0.26) and BADL (p = 0.46). The level of CVD severity did not appear to influence frontal lobe and parkinsonian assessments (p = 0.60). CONCLUSION: The contribution of CVD to the pathogenesis of various NPS is still debated. Our study, based on patients diagnosed with AD in a memory clinic setting, suggests that there is no relationship between the extent of CVD pathology and neuropsychiatric and behavioural measures in AD patients. Further prospective quantitative studies are needed to assess the role of CVD, if any, in neuropsychiatric and behavioural symptoms in AD. It is possible that the relatively small pathological contribution of CVD to the development of these symptoms is obscured by the effect of the wider neurodegeneration encountered in AD.