The brain undergoes many changes in chemistry and structure during normal aging. For example, it dries and shrinks. Neurons are lost from some regions and there is also neuronal atrophy and loss of synaptic branching. The extent of such losses remains controversial for all but a few subcortical regions of the brain. Decreases in glucose metabolism and in some pre-and post-synaptic neurotransmitter indices have also been reported. Many systems, however, remain entirely unexplored. The evidence to date also indicates that there is great regional specificity in the effects, and that humans show considerable variability between individuals. Of interest is the fact that some of the changes most clearly demonstrated in normal aging - such as loss of dopaminergic neurons of the substantia nigra and cholinergic neurons of the medial basal forebrain - also occur in a much accentuated form in neurodegenerative diseases such as Parkinson's disease and Alzheimer disease. The small loss of these systems in normal aging may account for the shuffling gait, stooped posture and memory loss in the elderly. A phenomenon seen in neurodegenerative diseases, but not in normal aging, is the appearance of chronic inflammation in the brain. The suggestion that the progress of such diseases might be slowed by treatment with anti-inflammatory agents has, in the case of Alzheimer disease, gained some support from 19 epidemiological studies and one very small clinical trial. Clearly more detailed clinical trials are required, and caution must be used because of the undesirable side effects of currently available anti-inflammatory agents.

The clock drawing test (CDT) is a widely used cognitive screening test. It is useful in identifying focal lesions and cognitive deficits in dementia groups. Lately, several studies attempted its use to differentiate between dementia subtypes. Although many studies have examined the CDT in dementia populations, research into the use of clock drawing in frontotemporal dementia (FTD) is limited. We examined quantitative (global) and qualitative (specific error type) differences on the CDT between FTD (n = 36) and Alzheimer's disease (AD; n = 25) patients and controls without dementia (n = 25). Results showed significantly lower overall scores in the dementia groups compared to the control group, whereas FTD patients scored significantly higher than the AD group. On qualitative analysis, the FTD group had fewer stimulus bound responses, conceptual deficits, and spatial or planning errors compared to the AD group. In conclusion, both global and error analysis of the CDT helped discriminate the FTD group from controls and AD patients. (JINS, 2006, 12, 159–165.)

The complement inflammatory cascade is an essential component of the phylogenetically ancient innate immune response and is crucial to our natural ability to ward off infection. Complement is involved in host defence by triggering the generation of a membranolytic complex (the C5b-9 complex) at the surface of the pathogen. Complement fragments (opsonins; C1q, C3b and iC3b) interact with complement cell-surface receptors (C1qRp, CR1, CR3 and CR4) to promote phagocytosis and a local pro-inflammatory response that, ultimately, contributes to the protection and healing of the host. Complement is of special importance in the brain, where entrance of elements of the adaptive immune system is restricted by a blood–brain barrier. There is now compelling evidence that complement is produced locally in response to an infectious challenge. Moreover, complement biosynthesis and activation also occurs in neurodegenerative disorders such as Alzheimer's, Huntington's and Pick's diseases, and the cytolytic/cytotoxic activities of complement are thought to contribute to neuronal loss and brain tissue damage. However, recent data suggest that at least some of the complement components have the ability to contribute to neuroprotective pathways. The emerging paradigm is that complement is involved in the clearance of toxic cell debris (e.g. amyloid fibrils) and apoptotic cells, as well as in promoting tissue repair through the anti-inflammatory activities of C3a. Knowledge of the unique molecular and cellular innate immunological interactions that occur in the development and resolution of pathology in the brain should facilitate the design of effective therapeutic strategies.

A personality and behavioral disorder is an important and defining feature of frontal lobe dementia (FLD) or frontotemporal degeneration (FTD). The diagnosis usually depends on the progressive development of various behavioral symptoms rather than a set of neuropsychological measures. Quantification of the personality–behavior disorder is important for standardizing the diagnosis. An inventory was constructed to capture the major positive and negative behaviors and personality change, and it was administered prospectively to caregivers of 108 patients in a cognitive neurology clinic, at the time of first diagnostic assessment. The prevalence and extent of behavioral abnormality was quantitated in the clinic population of FLD, vascular dementia (VaD), Alzheimer's disease (AD), primary progressive aphasia (PPA), and depressive disorder (DD) patients. The mean scores of FLD patients were significantly above all other groups. Scores in VaD were also higher than in AD, PPA, and DD. Interrater reliability (Cohen's kappa of .90) and item consistency (a Cronbach alpha of .89) were both high. Perseveration, indifference, inattention, inappropriateness, and loss of insight rated highest in FLD, significantly different from all other groups. Apathy, aspontaneity, inflexibility, disorganization, impulsivity, personal neglect, and poor judgment were also significantly higher in FLD. Discriminant function correctly classified 92.7% versus all other patients (NON-FLD) in the study. A total of 18.8% of VaD patients were misclassified as FLD. Indifference, alien hand, and inappropriateness were the highest discriminant functions. Perseveration and verbal apraxia were important discriminatory items for FLD and PPA, respectively. The FBI is a standardized behavioral inventory useful to diagnose FLD, to differentiate it from other dementias, and to quantify the behavior disorder. (JINS, 2000, 6, 460–468.)

A longitudinal case study of a patient with a progressive loss of meaning of objects with preserved phonology and syntax is presented. Repeated measures of language, praxis, visual cognition, and semantic processing were carried out. The patient still has preserved conversational speech, social skills, and orientation in her 8th year of her illness, but shows severe anomia and comprehension deficit in all modalities of stimulus presentation. In addition to standardized tests of language, cognition, and memory, specific experiments of categorization, modalities of word access, item consistency, category specificity, and definition of words were carried out. Results indicate a frequency dependent loss of meaning that was consistent in all modalities and throughout all object categories. However, the relative preservation of visual categorization of all categories tested and the language based categorization of animals suggested some fractionation of semantic memory. Relative preservation of autobiographical and personal memories versus semantic memory was a striking observation. Evidence for selective impairment of central semantic processing was obtained from experiments indicating item consistency of loss and the lack of semantic cuing. Neuroimaging evidence of left temporal lobe atrophy and the classical picture is compatible with similar cases published under the term semantic dementia or “transcortical sensory aphasia with visual agnosia” and suggest the diagnosis of Pick's disease. (JINS, 1998, 4, 388–398.)