Vikas Dhikav

Potential Predictors of Hippocampal Atrophy in Alzheimer's Disease

The hippocampus is a vulnerable and plastic brain structure that is damaged by a variety of stimuli, e.g. hypoxia, hypoperfusion, hypoglycaemia, stress and seizures. Alzheimer’s disease is a common and important disorder in which hippocampal atrophy is reported. Indeed, the available evidence suggests that hippocampal atrophy is the starting point of the pathogenesis of Alzheimer’s disease and a significant number of patients with hippocampal atrophy will develop Alzheimer’s disease. Studies indicate that hippocampal atrophy has functional consequences, e.g. cognitive impairment. Deposition of tau protein, formation of neurofibrillary tangles and accumulation of β-amyloid (Aβ) contributes to hippocampal atrophy together with damage caused by several other factors. Some of the factors associated with the development of hippocampal atrophy in Alzheimer’s disease have been identified, e.g. hypertension, diabetes mellitus, hyperlipidaemia, seizures, affective disturbances and stress, and more is being learnt about other factors.Hypertension can potentially damage the hippocampus through ischaemia caused by atherosclerosis and cerebral amyloid angiopathy. Diabetes can produce hippocampal lesions via both vascular and non-vascular pathologies and can reduce the threshold for hippocampal damage. Carriers of the apolipoprotein E (ApoE)-ɛ4 genotype have been shown to have greater mesial temporal atrophy and poorer memory functions than non-carriers. In addition to giving rise to abnormal lipid metabolism, the ApoE-ε4 allele can affect the course of Alzheimer’s disease via both Aβ-dependent and -independent pathways. Repetitive seizures can increase Aβ-peptide production and cause neurotransmission dysfunction and cytoskeletal abnormalities or a combination of these. Affective disturbances and stress are proposed to increase corticosteroid-induced hippocampal damage in many different ways.In the absence of any specific markers for predicting Alzheimer’s disease progression, it seems appropriate to learn more about the various predictors of hippocampal atrophy that determine the progression of Alzheimer’s disease from mild cognitive impairment (MCI), and then attempt to address these. It would be interesting to know to what extent these predictors play a role in the development of MCI or hasten the conversion of MCI to fullblown Alzheimer’s disease. Finally, it would be useful to know the extent to which these predictors can worsen or aggravate existing Alzheimer’s disease.Of the clinically used drugs in Alzheimer’s disease, anticholinesterases have been shown to slow down the rate of progression of hippocampal atrophy. One study observed that the neuroprotective effect of these agents is possibly due to an anti-Aβ effect produced by cholinergic stimulation. Similarly, antihypertensive and antihyperglycaemic drugs (pioglitazone and insulin) have been shown to reduce the risk of Alzheimer’s disease or disease progression. Currently, there are no disease-modifying therapies available for Alzheimer’s disease. It has been suggested that for treatment to be most effective, the regimen must be started before significant downstream damage has occurred (i.e. before the clinical diagnosis of Alzheimer’s disease, at the stage of MCI or earlier). Since the hippocampus is a plastic structure and atrophy of this structure is closely related to the pathophysiology of Alzheimer’s disease, if we could control blood pressure, regulate blood sugar, treat behavioural and psychological symptoms, achieve satisfactory lipid lowering and maintain a seizure-free state in patients with Alzheimer’s disease, this may not only improve disease control but could also potentially affect the rate of disease progression.

Depression in Dhat Syndrome

AIMS AND OBJECTIVES Dhat syndrome is a widely recognized clinical condition in the Indian subcontinent characterized by excessive preoccupation with semen loss as the main presenting complaint. This condition has been considered to be a culture-bound syndrome, and depressive symptoms have previously been reported. We were interested to know how common depression is, and to quantify these features. MATERIALS AND METHODS We studied 30 patients attending the Psychiatry Outpatient Department of a tertiary care hospital for their complaints about passing of semen in urine frequently. Those with depressive symptoms were further evaluated using the fourth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnostic Criteria for Depression, and depression severity was assessed using the 17-item Hamilton Depression Rating Scale for Depression (HAM-D). Patients meeting the criteria were started on capsule fluoxetine, a selective serotonin reuptake inhibitor, in dose of 20-40 mg per day. Patients were periodically followed fortnightly and were reevaluated for therapeutic response using the HAM-D. RESULTS A total of 30 patients (age = 20-40 years; mean age = 29 years; mean age of onset = 19 years; mean duration of illness = 11 months) were studied. The majority of cases were unmarried (64.2%) and educated till 5th class or above (70%). Twenty out of 30 (66%) patients met DSM-IV Diagnostic Criteria for Depression. Ten patients (33.3%) were found to have a comorbid problem of premature ejaculation, and two patients reported erectile dysfunction (6.6%). Patients showed statistically significant therapeutic response to fluoxetine. CONCLUSION Depressive phenomenology meeting DSM-IV Diagnostic Criteria for Depression seems common in Dhat syndrome and responds to selective serotonin reuptake inhibitors along with regular counseling.

Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

Introduction: Hippocampus undergoes atrophy in patients with Alzheimers disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materials and Methods: We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. Results: There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P> 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearsons correlation coefficient = −0.54;P< 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05). Conclusions: Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was higher compared to visual rating scores for MTL in patients with AD.