Prohovnik I, Perl D P, Davis K L, Libow L, Lesser G, Haroutunian V
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Neurology. 2006 Jan 10;66(1):49-55. doi: 10.1212/01.wnl.0000191298.68045.50.
Little is known about Alzheimer disease at advanced ages, although its incidence continues to increase at least through the ninth decade of life.
To examine the effects of age on the relationship between clinical dementia severity and neuropathologic hallmarks in a large sample spanning the full age range.
The authors assessed 81 subjects during life for dementia severity, and examined their brains. They analyzed plaque and tangle burden, as well as the activities of the cholinergic marker enzymes acetylcholinesterase (AChE) and choline acetyltransferase (ChAT), in relation to age at death and the clinical severity of dementia.
Dementia severity was strongly related to plaque and tangle burden in relatively young patients (aged < 75 years), but this correlation diminished with age and disappeared in the ninth decade of life. Among the oldest patients studied, there was no difference in plaque and tangle load between the mild and severe dementia cases. This interaction (p < 0.0001 for plaque density) was not observed for the cholinergic markers ChAT and AChE.
The nature or expression of Alzheimer disease may be different in severely demented older patients, who have equal cholinergic deficits but significantly lower plaque and tangle burden. If confirmed in a prospective study, these findings have diagnostic and therapeutic implications.
尽管阿尔茨海默病的发病率至少在九十岁之前持续上升，但对于高龄阶段的阿尔茨海默病我们知之甚少。
在一个涵盖所有年龄范围的大样本中，研究年龄对临床痴呆严重程度与神经病理学特征之间关系的影响。
作者在受试者生前评估了81名受试者的痴呆严重程度，并对他们的大脑进行了检查。他们分析了斑块和缠结负担，以及胆碱能标记酶乙酰胆碱酯酶（AChE）和胆碱乙酰转移酶（ChAT）的活性，这些分析与死亡年龄和痴呆的临床严重程度相关。
在相对年轻的患者（年龄<75岁）中，痴呆严重程度与斑块和缠结负担密切相关，但这种相关性随着年龄的增长而减弱，并在九十岁时消失。在研究的最年长患者中，轻度和重度痴呆病例之间的斑块和缠结负荷没有差异。对于胆碱能标记物ChAT和AChE，未观察到这种相互作用（斑块密度p<0.0001）。
在严重痴呆的老年患者中，阿尔茨海默病的性质或表现可能不同，这些患者有相同的胆碱能缺陷，但斑块和缠结负担明显较低。如果在前瞻性研究中得到证实，这些发现具有诊断和治疗意义。
